| + |
CDK4 | down-regulates 
phosphorylation
|
RB1 |
0.926 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135181 |
Ser249 |
AVIPINGsPRTPRRG |
Homo sapiens |
|
| pmid |
sentence |
| 15809340 |
Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-200483 |
Ser780 |
STRPPTLsPIPHIPR |
Homo sapiens |
|
| pmid |
sentence |
| 23336272 |
Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-200487 |
Ser795 |
SPYKFPSsPLRIPGG |
Homo sapiens |
|
| pmid |
sentence |
| 23336272 |
Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135185 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 15809340 |
Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-47899 |
Thr826 |
LPTPTKMtPRSRILV |
Homo sapiens |
|
| pmid |
sentence |
| 9139732 |
We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein. |
|
| Publications: |
5 |
Organism: |
Homo Sapiens |
| Pathways: | Pancreatic ductal adenocarcinoma (PDA) |
| + |
CDK1 | down-regulates
phosphorylation
|
RB1 |
0.673 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-21548 |
Ser249 |
AVIPINGsPRTPRRG |
Homo sapiens |
|
| pmid |
sentence |
| 1756735 |
The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-21552 |
Ser807 |
PGGNIYIsPLKSPYK |
Homo sapiens |
|
| pmid |
sentence |
| 1756735 |
The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-21556 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 1756735 |
The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-21560 |
Thr252 |
PINGSPRtPRRGQNR |
Homo sapiens |
|
| pmid |
sentence |
| 1756735 |
The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-21564 |
Thr373 |
VNVIPPHtPVRTVMN |
Homo sapiens |
|
| pmid |
sentence |
| 1756735 |
The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. |
|
| Publications: |
5 |
Organism: |
Homo Sapiens |
| + |
MAPK14 | down-regulates
phosphorylation
|
RB1 |
0.514 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168178 |
Ser567 |
SLAWLSDsPLFDLIK |
Homo sapiens |
|
| pmid |
sentence |
| 20871633 |
P38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates rb on ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not cdks, triggers an interaction between rb and the human homolog of murine double minute 2 (hdm2), leading to degradation of rb, release of e2f1 and cell death. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
CyclinE/CDK2 | down-regulates activity
phosphorylation
|
RB1 |
0.738 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250747 |
Ser608 |
TAADMYLsPVRSPKK |
|
C-33A Cell |
| pmid |
sentence |
| 10207050 |
In the present assay, ΔP3,4HA repressed E2F-mediated transcription similarly to wild-type pRB, suggesting that phosphorylation at other sites on ΔP3,4HA can disrupt its interaction with E2F and that these two sites are not sufficient to regulate E2F binding on DNA. This result is consistent with another report which showed that mutation of the human sites 8 and 9 (human Ser608 and Ser612) repressed E2F-mediated transcription to the same level as wild-type pRB (2). | Surprisingly, no one CDK site regulated the interaction of pRB with E2F when E2F was bound to DNA. Instead, disruption of transcriptional repression resulted from accumulation of phosphate groups on the RB molecule. |
|
| Publications: |
1 |
| Pathways: | FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, IGF and Myogenesis, p53 in cancer |
| + |
CHEK1 | up-regulates activity 
phosphorylation
|
RB1 |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-153904 |
Ser612 |
MYLSPVRsPKKKGST |
Homo sapiens |
|
| pmid |
sentence |
| 17380128 |
These results suggest that ser612 is phosphorylated by chk1/2 after dna damage, leading to the formation of prb-e2f-1. phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Cell cycle: G2/M phase transition |
| + |
CHEK2 | up-regulates activity
phosphorylation
|
RB1 |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-153908 |
Ser612 |
MYLSPVRsPKKKGST |
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 17380128 |
Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer |
| + |
CyclinD/CDK4 | down-regulates activity
phosphorylation
|
RB1 |
0.857 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216988 |
Ser780 |
STRPPTLsPIPHIPR |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 23336272 |
Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250759 |
Ser788 |
PIPHIPRsPYKFPSS |
in vitro |
|
| pmid |
sentence |
| 9139732 |
In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216992 |
Ser795 |
SPYKFPSsPLRIPGG |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 23336272 |
Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250760 |
Thr356 |
DSFETQRtPRKSNLD |
in vitro |
|
| pmid |
sentence |
| 9139732 |
In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250762 |
Thr5 |
tPRKTAAT |
in vitro |
|
| pmid |
sentence |
| 9139732 |
In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216957 |
Thr826 |
LPTPTKMtPRSRILV |
Homo sapiens |
|
| pmid |
sentence |
| 9139732 |
We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein. |
|
| Publications: |
6 |
Organism: |
Homo Sapiens, In Vitro |
| Pathways: | Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, IGF and Myogenesis, Pancreatic ductal adenocarcinoma (PDA), Rhabdomyosarcoma |
| + |
CTDSPL | up-regulates activity
dephosphorylation
|
RB1 |
0.306 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248304 |
Ser807 |
PGGNIYIsPLKSPYK |
Homo sapiens |
|
| pmid |
sentence |
| 15051889 |
ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248305 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 15051889 |
ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AMPK |
phosphorylation
|
RB1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216635 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 19217427 |
Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
CDK6 | down-regulates
phosphorylation
|
RB1 |
0.761 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135189 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 15809340 |
Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK5 | down-regulates
phosphorylation
|
RB1 |
0.343 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134468 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 15741232 |
Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKAA1 | down-regulates
phosphorylation
|
RB1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-184052 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 19217427 |
Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CyclinC/CDK3 | down-regulates activity
phosphorylation
|
RB1 |
0.426 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273181 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 15084261 |
The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK3 | down-regulates
phosphorylation
|
RB1 |
0.456 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124212 |
Ser811 |
IYISPLKsPYKISEG |
Homo sapiens |
|
| pmid |
sentence |
| 15084261 |
The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CyclinA2/CDK2 | down-regulates
phosphorylation
|
RB1 |
0.797 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217324 |
Thr821 |
KISEGLPtPTKMTPR |
Homo sapiens |
|
| pmid |
sentence |
| 9139732 |
We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK2 | down-regulates
phosphorylation
|
RB1 |
0.877 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-47895 |
Thr821 |
KISEGLPtPTKMTPR |
Homo sapiens |
|
| pmid |
sentence |
| 9139732 |
We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-176512 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21902831 |
Cycline/cdk2 blocks myod-induced gene expression through the phosphorylation of rb, preventing rb from binding and transactivating myod, and triggering s phase entry instead of differentiation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ABL1 |
phosphorylation
|
RB1 |
0.547 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-140396 |
Tyr805 |
RIPGGNIyISPLKSP |
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 16158058 |
Rb-induced apoptosis is compromised by abl-catalysed phosphorylation of rb at y805. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
CDKN1A | up-regulates activity 
|
RB1 |
0.703 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-69925 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10439039 |
P21 may inhibit cell cycle progression by preventing the phosphorylation of prb. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer, Rhabdomyosarcoma |
| + |
RB1 | down-regulates
binding
|
ABL1 |
0.547 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37139 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8242749 |
A domain in the c-terminus of rb, outside of the a/b pocket, binds to the atp-binding lobe of the c-abl tyrosine kinase, resulting in kinase inhibition. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
RB1 | up-regulates
binding
|
MYOD1 |
0.405 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-176563 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21902831 |
Cycline/cdk2 blocks myod-induced gene expression through the phosphorylation of rb, preventing rb from binding and transactivating myod, and triggering s phase entry instead of differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IGF and Myogenesis, Rhabdomyosarcoma |
| + |
MYOD1 | up-regulates quantity by expression
transcriptional regulation
|
RB1 |
0.405 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-238532 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 10373569 |
Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | IGF and Myogenesis, Rhabdomyosarcoma |
| + |
TLX1 | down-regulates activity
binding
|
RB1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-240725 |
|
|
Homo sapiens |
JURKAT Cell |
| pmid |
sentence |
| 15897879 |
ectopic HOX11 expression resulted in hyperphosphorylation of the retinoblastoma protein (Rb), which correlated with inhibition of the major Rb serine/threonine phosphatase PP1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RB1 | down-regulates 
|
Cell_cycle_progress |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267284 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21524151 |
Consistent with this, the magnitude of the response (i.e. the fraction of cells undergoing arrest) appears to diminish the closer the cells are to the time of S-phase entry. The existence of a time gap between full pRb phosphorylation and S-phase entry is also consistent with the notion that E2F, once released from pRb, transcriptionally activates factors needed for S-phase entry, a process which likely requires a significant amount of time. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK18 |
phosphorylation
|
RB1 |
0.291 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264558 |
|
|
in vitro |
|
| pmid |
sentence |
| 28361970 |
Activated PCTK3 phosphorylates retinoblastoma protein (Rb) in vitro. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
RB1 | up-regulates
|
Cell_cycle_block |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245486 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21524151 |
Consistent with this, the magnitude of the response (i.e. the fraction of cells undergoing arrest) appears to diminish the closer the cells are to the time of S-phase entry. The existence of a time gap between full pRb phosphorylation and S-phase entry is also consistent with the notion that E2F, once released from pRb, transcriptionally activates factors needed for S-phase entry, a process which likely requires a significant amount of time. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer |
| + |
RB1 | down-regulates activity
binding
|
E2F1 |
0.917 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37305 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8255752 |
E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Pancreatic ductal adenocarcinoma (PDA) |
| + |
RB1 | down-regulates
|
Proliferation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262533 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21524151 |
Consistent with this, the magnitude of the response (i.e. the fraction of cells undergoing arrest) appears to diminish the closer the cells are to the time of S-phase entry. The existence of a time gap between full pRb phosphorylation and S-phase entry is also consistent with the notion that E2F, once released from pRb, transcriptionally activates factors needed for S-phase entry, a process which likely requires a significant amount of time. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Luminal Breast Cancer, Malignant Melanoma, Pancreatic ductal adenocarcinoma (PDA), Rhabdomyosarcoma |
| + |
RB1 | down-regulates
binding
|
E2F2 |
0.91 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-197328 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22569856 |
Cyclin-dependent kinase (cdk) phosphorylation of the retinoblastoma protein (rb) drives cell proliferation through rb complexes with e2f transcription factors and other regulatory proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RB1 | down-regulates activity
binding
|
ANP32A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259083 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15716273 |
We further demonstrate that pp32-Rb interaction inhibits the apoptotic activity of pp32 and stimulates proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RB1 | up-regulates
|
HDAC3 |
0.604 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-118839 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14560017 |
We find that active rb mediates histone deacetylation on cyclin a, cdc2, topoisomerase iialfa, and thymidylate synthase promoters. We also demonstrate that this deacetylation is hdac dependent, since the hdac inhibitor trichostatin a (tsa) prevented histone deacetylation at each promoter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RB1 | down-regulates activity
binding
|
UBTF |
0.383 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262589 |
|
|
in vitro |
|
| pmid |
sentence |
| 7877691 |
Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PPP2CA | up-regulates
dephosphorylation
|
RB1 |
0.477 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-75398 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10702384 |
This dephosphorylation returns prb to its active, growth suppressive state. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RB1 | down-regulates
binding
|
TRIP11 |
0.329 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-50266 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9256431 |
The wild-type rb is able to interact with the rb-binding domain of trip230 / rb represses trip230-mediated activation of tr-regulated transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RB1 | up-regulates quantity by expression
transcriptional regulation
|
ITGA10 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253348 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 24287699 |
Integrin α10 expression is pRb-dependent in mouse osteoblasts|pRb-activated expression of integrin α10 mRNA is effectively translated into higher levels of integrin α10 protein as visualized by immunofluorescence |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
RB1 | down-regulates
|
G1/S_transition |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245483 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21524151 |
In its hypophosphorylated state, pRb binds transcription factors of the E2F family which are required for cell cycle progression. As the level of CyclinD/Cdk4/6 complexes increases, pRb becomes phosphorylated and progression through G1 occurs. At a critical level of phosphorylation, E2F is released from pRb. This activates the transcription of CyclinE which complexes with Cdk2 to fully release pRb repression by further phosphorylation, establishing a positive feedback loop. E2F further promotes the transcription of S-phase genes. Thus, CyclinD/Cdk4/6 and CyclinE/Cdk2 together regulate S-phase entry via phosphorylating pRb, which controls pRb binding to E2F |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA) |
| + |
CDKL1 | up-regulates activity
phosphorylation
|
RB1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273863 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28352193 |
We also proved that as a downstream molecule of the P15 pathway, Rb is inhibited after CDKL1 knockdown. Rb is a well-known tumor suppressor in cell cycle regulation.28 Phosphorylation of Rb negatively regulates the cell cycle through E2F repression.29–31 However, Rb contains 13 conserved sites that are phosphorylated by the CDK–P15 complex in cycling cells and phosphorylation will cause site-specific and diverse conformational changes in the complex.32,33 Further studies need to be conducted to decipher the phosphorylated site of Rb related to CDKL1 knockdown. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
RB1
- 
- 