| + |
MDM2 | up-regulates activity 
ubiquitination
|
NUB1 |
0.277 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278556 |
Lys159 |
KAMVLELkQSEEDAR |
Homo sapiens |
|
| pmid |
sentence |
| 28099510 |
Our results rather suggest that Mdm2 specifically ubiquitinates NUB1 on lysine 159 and that this modification is required for NUB1 functions.|We conclude that Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization 
ubiquitination
|
HDAC1 |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278761 |
Lys74 |
YHSDDYIkFLRSIRP |
Homo sapiens |
|
| pmid |
sentence |
| 26832969 |
MDM2 induces ubiquitination of HDAC1 in VSMCs.|Under calcification inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Prostate Cancer |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
RUNX3 |
0.576 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278557 |
Lys94 |
KTLPVAFkVVALGDV |
Homo sapiens |
|
| pmid |
sentence |
| 19808967 |
RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.|MDM2 suppresses the transcriptional activity of RUNX3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK1D | down-regulates
phosphorylation
|
MDM2 |
0.346 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167497 |
Ser118 |
NQQESSDsGTSVSEN |
Homo sapiens |
|
| pmid |
sentence |
| 20708156 |
Phosphorylation by casein kinase i promotes the turnover of the mdm2 oncoprotein via the scf(beta-trcp) ubiquitin ligase. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167501 |
Ser121 |
ESSDSGTsVSENRCH |
Homo sapiens |
|
| pmid |
sentence |
| 20708156 |
Phosphorylation by casein kinase i promotes the turnover of the mdm2 oncoprotein via the scf(beta-trcp) ubiquitin ligase. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167509 |
Ser246 |
DSVSDQFsVEFEVES |
Homo sapiens |
|
| pmid |
sentence |
| 20708156 |
Cki phosphorylates mdm2 at multiple sites to trigger mdm2/beta-trcp1 interactionbeta-trcp promotes mdm2 turnover and ubiquitination |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91195 |
Ser253 |
SVEFEVEsLDSEDYS |
Homo sapiens |
|
| pmid |
sentence |
| 12167711 |
Hypophosphorylation of mdm2 augments p53 stability. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167513 |
Ser253 |
SVEFEVEsLDSEDYS |
Homo sapiens |
|
| pmid |
sentence |
| 20708156 |
Cki phosphorylates mdm2 at multiple sites to trigger mdm2/beta-trcp1 interactionbeta-trcp promotes mdm2 turnover and ubiquitination |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91199 |
Ser262 |
DSEDYSLsEEGQELS |
Homo sapiens |
|
| pmid |
sentence |
| 12167711 |
Hypophosphorylation of mdm2 augments p53 stability. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167517 |
Ser262 |
DSEDYSLsEEGQELS |
Homo sapiens |
|
| pmid |
sentence |
| 20708156 |
Cki phosphorylates mdm2 at multiple sites to trigger mdm2/beta-trcp1 interactionbeta-trcp promotes mdm2 turnover and ubiquitination |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167520 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20708156 |
Phosphorylation by casein kinase i promotes the turnover of the mdm2 oncoprotein via the scf(beta-trcp) ubiquitin ligase. |
|
| Publications: |
8 |
Organism: |
Homo Sapiens |
| + |
AKT1 | up-regulates quantity by stabilization
phosphorylation
|
MDM2 |
0.81 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-116270 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 11504915 |
Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124949 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 15169778 |
Stabilization of mdm2 via decreased ubiquitination is mediated by protein kinase b/akt-dependent phosphorylation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
PIM1 | up-regulates quantity by stabilization
phosphorylation
|
MDM2 |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178615 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 18467333 |
Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD signaling |
| + |
PIM | up-regulates
phosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259433 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
Lymphoma Cell |
| pmid |
sentence |
| 18467333 |
Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259434 |
Ser186 |
RQRKRHKsDSISLSF |
Homo sapiens |
Lymphoma Cell |
| pmid |
sentence |
| 18467333 |
Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
AKT2 | up-regulates quantity by stabilization
phosphorylation
|
MDM2 |
0.558 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109732 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 11504915 |
Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DAPK3 | up-regulates quantity by stabilization
phosphorylation
|
MDM2 |
0.342 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-123159 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 15001356 |
Zip kinase was able to phosphorylate mdm2 at ser166, a site previously reported to be modified by akt kinase, thus demonstrating that zip kinase is a bona fide mdm2-binding protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PDXP | down-regulates activity
dephosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277151 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 33414453 |
Considering the roles of NF2 in actin dynamics and Mdm2 regulation - , , , it is noteworthy to elucidate whether interaction of PLPP and CIN with NF2 modulates actin dynamics and Mdm2 degradation in neuronal excitability.|Recently, we have reported that PLPP and CIN dephosphorylates Mdm2 at S166 site in activity dependent manners, which inhibits Mdm2 mediated PSD95 degradation by facilitating Mdm2 ubiquitination 38. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPKAPK2 | up-regulates quantity by stabilization
phosphorylation
|
MDM2 |
0.365 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-133560 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 15688025 |
Hdm2 phosphorylation by mapkap kinase 2 enhances hdm2 activity and promote the degradation of p53. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
AKT | up-regulates activity
phosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244296 |
Ser166 |
SSRRRAIsETEENSD |
Homo sapiens |
|
| pmid |
sentence |
| 15169778 |
Stabilization of mdm2 via decreased ubiquitination is mediated by protein kinase b/akt-dependent phosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244292 |
Ser186 |
RQRKRHKsDSISLSF |
Homo sapiens |
|
| pmid |
sentence |
| 11504915 |
Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244300 |
Ser188 |
RKRHKSDsISLSFDE |
Homo sapiens |
|
| pmid |
sentence |
| 15169778 |
Stabilization of mdm2 via decreased ubiquitination is mediated by protein kinase b/akt-dependent phosphorylationhere we show that pkb inhibits mdm2 self-ubiquitination via phosphorylation of mdm2 on ser(166) and ser(188) |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Triple mutant AML, NPM1_new, Prostate Cancer, Pancreatic ductal adenocarcinoma (PDA) |
| + |
AKT1 | up-regulates activity
phosphorylation
|
MDM2 |
0.81 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-116274 |
Ser186 |
RQRKRHKsDSISLSF |
Homo sapiens |
|
| pmid |
sentence |
| 11504915 |
Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
PIM1 | up-regulates
phosphorylation
|
MDM2 |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178619 |
Ser186 |
RQRKRHKsDSISLSF |
Homo sapiens |
Lymphoma Cell |
| pmid |
sentence |
| 18467333 |
Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD signaling |
| + |
AKT2 | up-regulates activity
phosphorylation
|
MDM2 |
0.558 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109736 |
Ser186 |
RQRKRHKsDSISLSF |
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 11504915 |
Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAK6 | up-regulates activity
phosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276427 |
Ser186 |
RQRKRHKsDSISLSF |
Homo sapiens |
|
| pmid |
sentence |
| 23132866 |
We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276428 |
Thr158 |
HLVSRPStSSRRRAI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23132866 |
We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AKT1 | up-regulates
phosphorylation
|
MDM2 |
0.81 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124953 |
Ser188 |
RKRHKSDsISLSFDE |
Homo sapiens |
|
| pmid |
sentence |
| 15169778 |
Stabilization of mdm2 via decreased ubiquitination is mediated by protein kinase b/akt-dependent phosphorylationhere we show that pkb inhibits mdm2 self-ubiquitination via phosphorylation of mdm2 on ser(166) and ser(188) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Kidney |
| Pathways: | FLT3-ITD signaling |
| + |
PLK1 | up-regulates
phosphorylation
|
MDM2 |
0.468 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-94272 |
Ser260 |
SLDSEDYsLSEEGQE |
Homo sapiens |
|
| pmid |
sentence |
| 12383858 |
Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188471 |
Ser260 |
SLDSEDYsLSEEGQE |
Homo sapiens |
|
| pmid |
sentence |
| 19833129 |
Polo-like kinase-1 phosphorylates mdm2 at ser260 and stimulates mdm2-mediated p53 turnover. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CSNK1D | down-regulates activity
phosphorylation
|
MDM2 |
0.346 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91191 |
Ser269 |
SEEGQELsDEDDEVY |
Homo sapiens |
|
| pmid |
sentence |
| 12167711 |
Hypophosphorylation of mdm2 augments p53 stability. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PP1 | up-regulates quantity by stabilization
dephosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264666 |
Ser370 |
KKTIVNDsRESCVEE |
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 23277204 |
Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP1CA | up-regulates quantity by stabilization
dephosphorylation
|
MDM2 |
0.357 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248566 |
Ser370 |
KKTIVNDsRESCVEE |
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 23277204 |
Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP1CC | up-regulates quantity by stabilization
dephosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248504 |
Ser370 |
KKTIVNDsRESCVEE |
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 23277204 |
Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP1CB | up-regulates quantity by stabilization
dephosphorylation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248577 |
Ser370 |
KKTIVNDsRESCVEE |
Homo sapiens |
|
| pmid |
sentence |
| 23277204 |
Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ATM | down-regulates activity
phosphorylation
|
MDM2 |
0.755 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188408 |
Ser386 |
DDKITQAsQSQESED |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 19816404 |
These data indicate that atm is responsible for directly phosphorylating s386 and s429 after dna damagemdm2 phosphorylation inhibits p53 poly ubiquitination |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158324 |
Ser395 |
SQESEDYsQPSTSSS |
Homo sapiens |
SAOS-2 Cell |
| pmid |
sentence |
| 17936559 |
Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-107256 |
Ser395 |
SQESEDYsQPSTSSS |
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 11331603 |
Atm phosphorylates mdm2 on s395 in vitro. Moreover, s395 appears to be phosphorylated in an atm-dependent manner in vivo the precise mechanism through which s395 phosphorylation attenuates mdm2 function is unclear. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-94268 |
Ser395 |
SQESEDYsQPSTSSS |
in vitro |
|
| pmid |
sentence |
| 12383858 |
Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188412 |
Ser429 |
KEESVESsLPLNAIE |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 19816404 |
These data indicate that atm is responsible for directly phosphorylating s386 and s429 after dna damagemdm2 phosphorylation inhibits p53 poly ubiquitination |
|
| Publications: |
5 |
Organism: |
Homo Sapiens, In Vitro |
| Pathways: | FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer |
| + |
PPM1D | up-regulates
dephosphorylation
|
MDM2 |
0.68 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158328 |
Ser395 |
SQESEDYsQPSTSSS |
Homo sapiens |
|
| pmid |
sentence |
| 17936559 |
Wip1 interacts with and dephosphorylates mdm2 at serine 395, a site phosphorylated by the atm kinase. Dephosphorylated mdm2 has increased stability and affinity for p53, facilitating p53 ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPM1D | down-regulates quantity by destabilization
dephosphorylation
|
MDM2 |
0.68 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248324 |
Ser395 |
SQESEDYsQPSTSSS |
Homo sapiens |
|
| pmid |
sentence |
| 17936559 |
Here we show that the wild-type p53-induced phosphatase 1 (Wip1), or PPM1D, downregulates p53 protein levels by stabilizing Mdm2 and facilitating its access to p53. Wip1 interacts with and dephosphorylates Mdm2 at serine 395, a site phosphorylated by the ATM kinase. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ATR | down-regulates activity
phosphorylation
|
MDM2 |
0.519 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-119546 |
Ser407 |
SSSIIYSsQEDVKEF |
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 14654783 |
We found that a major kinase responsible for s407 phosphorylation is atrs407 phosphorylation of mdm2 by atr reduces mdm2-dependent export of p53 from nuclei to cytoplasm. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer |
| + |
PPP2CB | up-regulates
dephosphorylation
|
MDM2 |
0.396 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-86736 |
Thr216 |
RSSSSEStGTPSNPD |
Homo sapiens |
|
| pmid |
sentence |
| 11983168 |
Cyclin g also binds in vivo and in vitro to mdm2 and markedly stimulates the ability of pp2a to dephosphorylate mdm2 at t216. Our data imply that the function of cyclin g is to serve as a negative regulator of p53 by activating mdm2 through dephosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP2CB | up-regulates activity
dephosphorylation
|
MDM2 |
0.396 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248593 |
Thr216 |
RSSSSEStGTPSNPD |
Mus musculus |
|
| pmid |
sentence |
| 11983168 |
cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PPP2CA | up-regulates activity
dephosphorylation
|
MDM2 |
0.451 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248636 |
Thr216 |
RSSSSEStGTPSNPD |
Mus musculus |
|
| pmid |
sentence |
| 11983168 |
cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ABL1 | down-regulates
phosphorylation
|
MDM2 |
0.715 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169699 |
Tyr276 |
SDEDDEVyQVTVYQA |
Homo sapiens |
|
| pmid |
sentence |
| 21081495 |
Mdm2 has three known c-abl phosphorylation sites (tyr276, tyr394, and tyr405)these data show that c-abl is important for reducing mdm2 and mdmx protein levels after genotoxic stress and suggest another cellular mechanism for the stabilization and activation of p53. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169703 |
Tyr405 |
STSSSIIySSQEDVK |
Homo sapiens |
|
| pmid |
sentence |
| 21081495 |
Mdm2 has three known c-abl phosphorylation sites (tyr276, tyr394, and tyr405)these data show that c-abl is important for reducing mdm2 and mdmx protein levels after genotoxic stress and suggest another cellular mechanism for the stabilization and activation of p53. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
ABL1 | down-regulates activity
phosphorylation
|
MDM2 |
0.715 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-90512 |
Tyr394 |
QSQESEDySQPSTSS |
Homo sapiens |
|
| pmid |
sentence |
| 12110584 |
C-abl binds and phosphorylates mdm2 in vivo and in vitro;phosphorylation of mdm2 by c-abl impairs the inhibition of p53 by mdm2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
MDM2 | down-regulates
ubiquitination
|
NUMB |
0.446 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-99497 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 12646252 |
These data strongly suggest thatmdm2functions as the ubiquitin ligase toward hnumb and that it induces its degradation in intact cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NfKb-p65/p50 | up-regulates quantity by expression 
transcriptional regulation
|
MDM2 |
0.373 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168296 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20921405 |
Nf-kb activation following t-cell receptor engagement induces the expression of mdm2 through interaction with nf-kb sites in its p1 promoter |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD signaling, Pancreatic ductal adenocarcinoma (PDA) |
| + |
FBXO31 | down-regulates quantity by destabilization
binding
|
MDM2 |
0.324 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277380 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 29343641 |
FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
polyubiquitination, ubiquitination
|
POLQ |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272729 |
|
|
Homo sapiens |
RKO Cell |
| pmid |
sentence |
| 22056306 |
DNA polymerase eta is targeted by Mdm2 for polyubiquitination and proteasomal degradation in response to ultraviolet irradiation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278827 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22056306 |
In addition, we showed that Mdm2 is able to promote the PolH ubiquitination and degradation.|In contrast, ectopically expression of Mdm2 decreases PolH expression, which can be abrogated by the proteasome inhibitor MG132. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
RFWD3 | up-regulates activity
binding
|
MDM2 |
0.366 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271945 |
|
|
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 20173098 |
RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates activity
ubiquitination
|
FOXO4 |
0.628 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278656 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18665269 |
Mdm2 Induces Mono-Ubiquitination of FOXO4.|higher amounts of Mdm2 transfected resulted in reduced FOXO4 transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FHIT | down-regulates 
|
MDM2 |
0.43 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-127610 |
|
|
Homo sapiens |
Lung Cancer Cell |
| pmid |
sentence |
| 15313915 |
We found that this synergistic inhibition of tumor cell growth corresponded with the fhit-mediated inactivation of mdm2, which thereby blocked the association of mdm2 with p53, thus stabilizing the p53 protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pancreatic ductal adenocarcinoma (PDA) |
| + |
MDM2 | down-regulates quantity by repression
|
CDKN1A |
0.647 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160977 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18292944 |
Overexpression of hdm2 resulted in a decrease in the level of p21waf1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer |
| + |
NUMB | down-regulates
binding
|
MDM2 |
0.446 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168454 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20940030 |
Numb interacts with mdm2, and inhibits its ubiquitin-ligase function on tp53 (which in itself is inhibitory for tp53), thus numb activates (b) tp53 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
RPL26 |
0.501 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278828 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18951086 |
In addition, Mdm2 ubiquitylates L26, leading to its proteasome-mediated degradation.|We now report that Mdm2 regulates p53 levels also by targeting ribosomal protein L26. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BCL3 | up-regulates quantity by expression
transcriptional regulation
|
MDM2 |
0.287 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143403 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16384933 |
One mechanism by which this inhibition occurs is through bcl-3-mediated induction of the p53 inhibitor hdm2. Both stable and transient overexpression of bcl-3 leads to increased hdm2 expression, and small interfering rna (sirna)-mediated knockdown of bcl-3 blocks expression of hdm2. ( articolo-abstract) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
OVOL2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278826 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 35896951 |
In breast cancer cells, MDM2 overexpression or p53 KD reduced OVOL2 protein expression, and the proteasome inhibitor MG132 blocked the MDM2 overexpression\u2010 or p53 KD\u2010mediated reduction in OVOL2 expression (Figure\u00a06B,C).|The E3 ubiquitin ligase MDM2 ubiquitinates and degrades the OVOL2 protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
TP53 |
0.968 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-196116 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22337874 |
The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199371 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23150757 |
Dual Roles of MDM2 in the Regulation of p53: Ubiquitination Dependent and Ubiquitination Independent Mechanisms of MDM2 Repression of p53 Activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-80528 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10935507 |
Many posttranslational modifications of p53, such as phosphorylation, dephosphorylation, acetylation and ribosylation, have been shown to occur following cellular stress. Some of these modifications may activate the p53 protein, interfere with MDM2 binding and/or dictate cellular localization of p53. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, IDH-TET in AML, miRNA in AML, NPM1 in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Triple mutant AML, NPM1_new, Prostate Cancer, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA) |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
PPARG |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277191 |
|
|
Homo sapiens |
SW-480 Cell |
| pmid |
sentence |
| 26718225 |
Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Prostate Cancer |
| + |
Serdemetan | down-regulates
chemical inhibition
|
MDM2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-193504 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DAXX | up-regulates
binding
|
MDM2 |
0.672 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-200892 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23405218 |
The optimal function of mdm2 requires daxx, which stabilizes mdm2 through the deubiquitinase hausp/usp7 and also directly promotes mdm2's ubiquitin ligase activity towards p53. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
KAT2B |
0.619 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278825 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14769800 |
Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
IER3 |
0.35 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278824 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26973248 |
FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TFAP4 | down-regulates quantity by repression
transcriptional regulation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-226596 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 19505873 |
AP-4 Mediates E-box-dependent Complex Formation for Transcriptional Repression of HDM2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDKN2A | down-regulates activity
relocalization
|
MDM2 |
0.765 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-192697 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23416275 |
We propose that p14(arf) increases the binding of p53-mdm2 complexes to chromatin, thereby limiting the access of protein deacetylases to p53. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, NPM1 in AML, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Malignant Melanoma, Triple mutant AML, NPM1_new |
| + |
nutlin-3A | down-regulates
chemical inhibition
|
MDM2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194874 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates
binding
|
EP300 |
0.686 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-84077 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 11070080 |
Mdm2, a negative-feedback regulator of p53, inhibited p300-mediated p53 acetylation by complexing with these two proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, p53 in cancer |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
ATXN1 |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278823 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28212558 |
NICD and MDM2 ubiquitinate and degrade ATXN1.|These results suggest that NICD and MDM2 synergistically reduce ATXN1 expression at the posttranscriptional level. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
ASF1A |
0.268 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278822 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26336826 |
We found that MDM2 overexpression also decreased the ASF1A half-life time, indicating an accelerated ASF1A degradation.|We next examined whether the presence of RAD6 is essential for MDM2-induced ASF1A ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
RPL6 |
0.434 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278630 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24174547 |
Furthermore, we also demonstrated that RPL6 is a substrate for HDM2-mediated ubiquitination and proteasomal degradation.|The interaction of RPL6 and HDM2 drives HDM2 mediated RPL6 polyubiquitination and proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
APEX1 |
0.417 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278555 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21727086 |
Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TP53 | up-regulates quantity by expression
transcriptional regulation
|
MDM2 |
0.968 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-34962 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 7958853 |
The p53 tumor suppressor protein trans-activates mdm2 itself, which is therefore considered a component of a p53 negative feedback loop. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, IDH-TET in AML, miRNA in AML, NPM1 in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Triple mutant AML, NPM1_new, Prostate Cancer, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA) |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
RB1 |
0.666 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278530 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15577944 |
In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA) |
| + |
SRSF2 | up-regulates quantity by expression
transcriptional regulation
|
MDM2 |
0.28 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260076 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27524244 |
Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, IDH-TET in AML |
| + |
MDM2 | down-regulates quantity by destabilization
binding
|
CDKN1A |
0.647 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272954 |
|
|
Homo sapiens |
PC-3 Cell |
| pmid |
sentence |
| 14761977 |
MDM2 facilitates p21 degradation independent of ubiquitination and the E3 ligase function of MDM2. Instead, MDM2 promotes p21 degradation by facilitating binding of p21 with the proteasomal C8 subunit. The physical interaction between p21 and MDM2 was demonstrated both in vitro and in vivo with the binding region in amino acids 180-298 of the MDM2 protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer |
| + |
MDM2 | down-regulates activity
binding
|
TP73 |
0.836 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255470 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17700533 |
Since HDM2, a key negative regulator of p53, also binds to and inhibits p73, we asked whether p73 could mediate Nutlin-3-induced apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PYHIN1 | down-regulates quantity by destabilization
binding
|
MDM2 |
0.416 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268493 |
|
|
Homo sapiens |
MDA-MB-468 Cell |
| pmid |
sentence |
| 16479015 |
Here, we show that IFIXalpha1 downregulates HDM2, a principal negative regulator of p53, at the posttranslational level. IFIXalpha1 destabilizes HDM2 protein and promotes its ubiquitination. The E3 ligase activity of HDM2 appears to be required for this IFIXalpha1 effect. Importantly, HDM2 downregulation is required for the IFIXalpha1-mediated increase of p53 protein levels, transcriptional activity, and nuclear localization, suggesting that IFIXalpha1 positively regulates p53 by acting as a negative regulator of HDM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271042 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34199813 |
The ubiquitination process is mediated sequentially by three classes of enzymes consisting of a Ub-activating enzyme E1, a Ub-conjugating enzyme E2, and a Ub ligase E3. Ub is first activated by E1 in an adenosine 5′-triphosphate (ATP)-dependent manner t |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM28 | up-regulates activity
binding
|
MDM2 |
0.596 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-240405 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16107876 |
we present evidence that MDM2 interacts with the nuclear corepressor KAP1. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity
ubiquitination
|
SIRT6 |
0.417 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278702 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25074979 |
These results suggest that MDM2 degrades SIRT6 in a proteasome dependent manner.|USP10 has been shown to deubiquitinate and stabilize p53, a well-known substrate of MDM2, suggesting a mechanism whereby SIRT6 is ubiquitinated and destabilized by MDM2, which could be reversed by USP10 mediated deubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDKN2AIP | down-regulates quantity by repression
transcriptional regulation
|
MDM2 |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160971 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18292944 |
Carf interacts with hdm2 and undergoes degradation by an hdm2-dependent proteasome pathway, and ii) it acts as a transcriptional repressor of hdm2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
polyubiquitination
|
EID1 |
0.425 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272582 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 11073989 |
Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
G3BP2 | down-regulates activity
binding
|
MDM2 |
0.3 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278892 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 17297477 |
G3BP2 binds to MDM2 and decreases its E3 ligase activity. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM4 | up-regulates quantity by stabilization
binding
|
MDM2 |
0.73 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272932 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10218570 |
MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates activity
binding
|
GNAS |
0.396 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278070 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18948082 |
Western blotting showed that increased MDM2 expression decreased Gαs protein content in HEK293 cells (Fig. 4B). Taken together, these data indicate that MDM2 binds to Gαs and has a direct impact on Gαs protein content. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | up-regulates activity
ubiquitination
|
HEXIM1 |
0.468 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278701 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19617712 |
Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity
ubiquitination
|
ARRB2 |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278760 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21389118 |
Indeed, the ubiquitination of \u03b2-arrestin2 by Mdm2 H457S was severely reduced in comparison to Mdm2 wt ( xref ).|Loss of Mdm2 E3 ligase activity causes dominant nuclear localization of beta-arrestin2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FEZF2 | down-regulates quantity by repression
transcriptional regulation
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268974 |
|
|
|
|
| pmid |
sentence |
| 23677067 |
FEZF2, a novel 3p14 tumor suppressor gene, represses oncogene EZH2 and MDM2 expression and is frequently methylated in nasopharyngeal carcinoma. |
|
| Publications: |
1 |
| + |
MDM2 | down-regulates quantity
ubiquitination
|
NFATC2 |
0.307 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278657 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24777531 |
MDM2 negatively regulates NFATc2 and T cell activation.|The E3 ubiquitin ligase MDM2 is known to induce NFATc2 ubiquitination in a breast cancer cell line 24. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | up-regulates activity
polyubiquitination
|
DDX24 |
0.335 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272845 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 24980433 |
MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
USP7 | up-regulates
deubiquitination
|
MDM2 |
0.77 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-139450 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16082221 |
Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BTK | down-regulates activity
phosphorylation
|
MDM2 |
0.279 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278330 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29290977 |
Phosphorylation of MDM2 by BTK suppresses its ubiquitination activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates
ubiquitination
|
NOTCH4 |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-172826 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21402876 |
We demonstrate that the intracellular domain of notch 4 is targeted for ubiquitylation and hence degradation by the ubiquitin ligase mdm2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Breast |
| + |
MDM2 | down-regulates quantity by destabilization
polyubiquitination
|
KAT5 |
0.652 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272613 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 11927554 |
Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, IDH-TET in AML |
| + |
FBXO22 | down-regulates quantity by destabilization
ubiquitination
|
MDM2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273440 |
|
|
Homo sapiens |
Breast Cancer Cell Line |
| pmid |
sentence |
| 31138683 |
SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | up-regulates quantity by stabilization
ubiquitination
|
MDM2 |
0.468 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278769 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25088038 |
NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ]. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates
ubiquitination
|
MDM4 |
0.73 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-144970 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16511560 |
The mdm2 homolog mdmx is an important regulator of p53 during mouse embryonic development. Dna damage promotes mdmx phosphorylation, nuclear translocation, and degradation by mdm2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 1-RBX1-Skp1 | down-regulates quantity by destabilization
ubiquitination
|
MDM2 |
0.381 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273441 |
|
|
Homo sapiens |
Breast Cancer Cell Line |
| pmid |
sentence |
| 31138683 |
SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM4 | up-regulates quantity by stabilization
|
MDM2 |
0.73 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134391 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15735705 |
Mdm2 and mdmx function as cellular regulators of the p53 tumor suppressor protein. Intriguingly, the activities of these proteins are interdependent;mdmx stabilizes mdm2, enabling its activities towards p53 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
polyubiquitination
|
PER2 |
0.358 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277421 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30425162 |
We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
SUV39H1 |
0.402 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278631 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23376847 |
A recent report showed that the p53 inducible E3 ligase MDM2 causes SUV39H1 degradation.|Furthermore, it was reported that MDM2 can ubiquitinate and degrade SUV39H1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates
ubiquitination
|
CDKN2AIP |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160974 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18292944 |
Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
GRK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278629 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 33806062 |
Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.|Our results show now that EGF-induced phosphorylation of GRK2 on S670 is a key event in initiating centrosome separation and also a relevant clue for limiting centrosome separation, as this event simultaneously triggers the Mdm2-dependent ubiquitination and degradation of GRK2 ( xref ). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
HIF1A |
0.641 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271385 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 10640274 |
We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity
ubiquitination
|
IRF1 |
0.389 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278590 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27795392 |
HIV-1 Tat Recruits HDM2 E3 Ligase To Target IRF-1 for Ubiquitination and Proteasomal Degradation.|IRF-1 ubiquitination by HDM2 is specifically increased during HIV-1 infection in the presence of increasing amounts of Tat and is mediated by the formation of a trimeric complex between Tat, IRF-1, and HDM2, as demonstrated by coimmunoprecipitation analysis (XREF_FIG). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ELF4 | up-regulates quantity by expression
transcriptional regulation
|
MDM2 |
0.384 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-185490 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19380490 |
We found that elf4/mef activates mdm2 expression |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | up-regulates
ubiquitination
|
NOTCH1 |
0.479 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-200197 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23252402 |
Although the interaction between notch1 and mdm2 results in ubiquitination of notch1, this does not result in degradation of notch1, but instead leads to activation of the intracellular domain of notch1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD signaling |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
IGF1R |
0.66 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278571 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12821780 |
We could prove that Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NAT10 | down-regulates quantity by destabilization
ubiquitination
|
MDM2 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272405 |
|
|
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 26882543 |
NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM13 | down-regulates quantity by destabilization
polyubiquitination
|
MDM2 |
0.375 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271851 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21333377 |
Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT. We observed that RFP2 formed a complex with MDM2, a negative regulator of the p53 tumor suppressor, and AKT, a regulator of apoptosis inhibition at the cellular level. Additionally, we found that the interaction of RFP2 with MDM2 and AKT resulted in ubiquitination and proteasomal degradation of MDM2 and AKT in vivo and in vitro. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
ubiquitination
|
DYRK2 |
0.567 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275579 |
|
|
|
|
| pmid |
sentence |
| 19965871 |
Under normal conditions, nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation.|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus. |
|
| Publications: |
1 |
| + |
ARRB2 | up-regulates quantity by stabilization
binding
|
MDM2 |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272592 |
|
|
Homo sapiens |
SAOS-2 Cell |
| pmid |
sentence |
| 12488444 |
Our current results demonstrated that the binding of Mdm2 to beta-arrestin 2 was significantly enhanced by stimulation of GPCRs. Activation of GPCRs led to formation of a ternary complex of Mdm2, beta-arrestin 2, and GPCRs and thus recruited Mdm2 to GPCRs at plasma membrane. Moreover, the binding of beta-arrestin 2 to Mdm2 suppressed the self-ubiquitination of Mdm2 and consequently reduced the Mdm2-mediated p53 degradation and ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
polyubiquitination
|
PBXIP1 |
0.29 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272850 |
|
|
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 24488098 |
. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
MDM2
- 
- 