| + |
CSNK1A1 | up-regulates 
phosphorylation
|
MDM4 |
0.379 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199015 |
Ser289 |
DDLEDSKsLSDDTDV |
Homo sapiens |
|
| pmid |
sentence |
| 23028042 |
Previous studies showed that casein kinase 1? (ck1?) Stably associates with mdmx, stimulates mdmx-p53 binding, and cooperates with mdmx to inactivate p53ck1? Binding to the mdmx central domain and phosphorylation of s289 disrupts the intramolecular interaction, allowing the n terminus to bind p53 with increased affinity. After dna damage, the mdmx-ck1? Complex is disrupted by chk2-mediated phosphorylation of mdmx at s367, leading to reduced mdmx-p53 binding. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CHEK2 | down-regulates 
phosphorylation
|
MDM4 |
0.712 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-140417 |
Ser342 |
SKLTHSLsTSDITAI |
Homo sapiens |
|
| pmid |
sentence |
| 16163388 |
Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ATM | down-regulates
phosphorylation
|
MDM4 |
0.725 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-149292 |
Ser342 |
SKLTHSLsTSDITAI |
Homo sapiens |
|
| pmid |
sentence |
| 16943424 |
Recently we showed that atm- and hdm2-dependent ubiquitination and subsequent degradation of hdmx following dsb induction are mediated by phosphorylation of hdmx on s403, s367, and s342, with s403 being targeted directly by atm. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-149300 |
Ser403 |
DLAHSSEsQETISSM |
Homo sapiens |
|
| pmid |
sentence |
| 16943424 |
Recently we showed that atm- and hdm2-dependent ubiquitination and subsequent degradation of hdmx following dsb induction are mediated by phosphorylation of hdmx on s403, s367, and s342, with s403 being targeted directly by atm. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-139403 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16082221 |
Atm directly and indirectly induces mdm2 and mdmx phosphorylation, resulting in decreased activity and stability of these proteins. We recently provided a mechanism for the reduced stability of mdm2 and mdmx by showing that atm-dependent phosphorylation lowers their affinity for the deubiquitinating enzyme hausp. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CHEK1 | down-regulates activity
phosphorylation
|
MDM4 |
0.541 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250770 |
Ser342 |
SKLTHSLsTSDITAI |
Homo sapiens |
SAOS-2 Cell |
| pmid |
sentence |
| 16163388 |
MDMX is a direct substrate for Chk1 and Chk2 in vitro. Phosphorylation of MDMX leads to increased binding to MDM2 and more efficient ubiquitination, providing an explanation for the enhanced degradation of MDMX after DNA damage. | Western blot showed that Chk1 modified S342 and S367, but with strong preference for S342. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ATM | down-regulates quantity by destabilization
phosphorylation
|
MDM4 |
0.725 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-149296 |
Ser367 |
PDCRRTIsAPVVRPK |
Homo sapiens |
|
| pmid |
sentence |
| 16943424 |
Recently we showed that atm- and hdm2-dependent ubiquitination and subsequent degradation of hdmx following dsb induction are mediated by phosphorylation of hdmx on s403, s367, and s342, with s403 being targeted directly by atm. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT1 | up-regulates quantity by stabilization
phosphorylation
|
MDM4 |
0.528 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252517 |
Ser367 |
PDCRRTIsAPVVRPK |
Homo sapiens |
|
| pmid |
sentence |
| 18356162 |
We demonstrate that the serine/threonine kinase akt mediates phosphorylation of mdmx at ser367. This phosphorylation leads to stabilization of mdmx and consequent stabilization of mdm2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT | up-regulates activity
phosphorylation
|
MDM4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178063 |
Ser367 |
PDCRRTIsAPVVRPK |
Homo sapiens |
|
| pmid |
sentence |
| 18356162 |
We demonstrate that the serine/threonine kinase akt mediates phosphorylation of mdmx at ser367. This phosphorylation leads to stabilization of mdmx and consequent stabilization of mdm2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CHEK2 | down-regulates quantity by destabilization
phosphorylation
|
MDM4 |
0.712 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178071 |
Ser367 |
PDCRRTIsAPVVRPK |
Homo sapiens |
|
| pmid |
sentence |
| 18356162 |
The chk1 and chk2 kinases have also been shown to phosphorylate ser367, leading to 14-3-3 binding (34_36, 38, 44). In both cases, the outcome differed: in chk1-mediated phosphorylation, mdmx was translocated to the cytoplasm;in chk2-mediated phosphorylation, mdmx was degraded (34_36, 38, 44). It is possible that the damage response is mediated through additional phosphorylation sites other than ser367 and that, depending on the type of damage, certain sites will be modified, leading to different outcomes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CHEK1 | down-regulates quantity by destabilization
phosphorylation
|
MDM4 |
0.541 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178067 |
Ser367 |
PDCRRTIsAPVVRPK |
Homo sapiens |
|
| pmid |
sentence |
| 18356162 |
The chk1 and chk2 kinases have also been shown to phosphorylate ser367, leading to 14-3-3 binding (34_36, 38, 44). In both cases, the outcome differed: in chk1-mediated phosphorylation, mdmx was translocated to the cytoplasm;in chk2-mediated phosphorylation, mdmx was degraded (34_36, 38, 44). It is possible that the damage response is mediated through additional phosphorylation sites other than ser367 and that, depending on the type of damage, certain sites will be modified, leading to different outcomes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPM1D | up-regulates quantity by stabilization
dephosphorylation
|
MDM4 |
0.45 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275491 |
Ser403 |
DLAHSSEsQETISSM |
|
|
| pmid |
sentence |
| 33309518 |
PPM1D also inhibits p53 activity by dephosphorylating Ser395 and stabilizing MDM2 and by dephosphorylating Ser403 on MDMX |
|
| Publications: |
1 |
| + |
CDK1 | down-regulates
phosphorylation
|
MDM4 |
0.418 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134388 |
Ser96 |
SFSVKDPsPLYDMLR |
Homo sapiens |
|
| pmid |
sentence |
| 15735705 |
Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
USP7 | up-regulates
deubiquitination
|
MDM4 |
0.747 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-139453 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16082221 |
Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates
ubiquitination
|
MDM4 |
0.714 |
| 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 |
| + |
58131-57-0 | down-regulates
chemical inhibition
|
MDM4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194856 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM4 | up-regulates quantity by stabilization 
|
MDM2 |
0.714 |
| 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 |
| + |
MDM4 | down-regulates quantity by destabilization
ubiquitination
|
MDM4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271390 |
|
|
in vitro |
|
| pmid |
sentence |
| 12393902 |
Here we demonstrate that MdmX acts as a ubiquitin ligase in vitro, being capable of autoubiquitination, as well as mediating the ubiquitination of p53. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
58131-57-0 | down-regulates activity
chemical inhibition
|
MDM4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262246 |
|
|
in vitro |
|
| pmid |
sentence |
| 21075910 |
Here we report the identification of a benzofuroxan derivative [7-(4-methylpiperazin-1-yl)-4-nitro-1-oxido-2,1,3-benzoxadiazol-1-ium, NSC207895] that could inhibit MDMX expression in cancer cells through a reporter-based drug screening. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
MDM4 | down-regulates quantity by destabilization
ubiquitination
|
TP53 |
0.947 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271389 |
|
|
in vitro |
|
| pmid |
sentence |
| 12393902 |
Here we demonstrate that MdmX acts as a ubiquitin ligase in vitro, being capable of autoubiquitination, as well as mediating the ubiquitination of p53. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
MDM4 | up-regulates quantity by stabilization
binding
|
MDM2 |
0.714 |
| 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 |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
MDM4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271129 |
|
|
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 |
3.0
MDM4
- 
- 