IndraLab

"Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site."

"ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms."

"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."

"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."

"Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site."

"The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition."

"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)."

"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."

"Inactivation of pRb occurs through its gradual phosphorylation by Cdks during the G1 phase of the cell division cycle resulting in the activation of transcription factors that promote cell proliferation and enable transition on to the S phase (see ref. 11 for review)."

"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."

"This dephosphorylation returns prb to its active, growth suppressive state."

"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."

"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."

"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."

"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."

"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."

"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."

"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."

"ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms."

"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."

"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."

"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."

"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."

"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 (Fig. ​(Fig.5C).5C). 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."

"In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB."

"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."

"In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB."

"ectopic HOX11 expression resulted in hyperphosphorylation of the retinoblastoma protein (Rb), which correlated with inhibition of the major Rb serine/threonine phosphatase PP1."

"In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB."

"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."

"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."

"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."

"Although the receptor-selective retinoids induce minimal amounts of apoptosis in T47D breast cancer cells, the predominant factor that leads to growth arrest is G1 cell cycle blockade. Our data indicate that this blockade results from the downregulation of Cyclin D1 and Cyclin D3, which in turn causes Rb hypophosphorylation."

"<E7> E2F-DP dimers, complexed with pRb, p107, or p130, can bind and inhibit E2 promoter elements (Dyson, 1998; Mayol and Grana, 1998). In quiescent cells, the predominant complexes contain E2F4 and p130. E2F1_DP:RB1-|taof(E2F1_DP) E2F2_DP:RB1-|taof(E2F2_DP) E2F3_DP:RB1-|taof(E2F3_DP) E2F4_DP:RB1-|taof(E2F4_DP) E2F1_DP:RBL1-|taof(E2F1_DP) E2F2_DP:RBL1-|taof(E2F2_DP) E2F3_DP:RBL1-|taof(E2F3_DP) E2F4_DP:RBL1-|taof(E2F4_DP) E2F1_DP:NOLC1-|taof(E2F1_DP) E2F2_DP:NOLC1-|taof(E2F2_DP) E2F3_DP:NOLC1-|taof(E2F3_DP) E2F4_DP:NOLC1-|taof(E2F4_DP)"

"The sensitivity of the Rb phosphatase in intact cells to various cell-permeable cytotoxins also points to PP1 (396). D. Exit From the Pachytene Stage in Yeast Meiosis In yeast, a premature exit from the pachytene stage after the initiation of meiotic recombination is prevented by the so-called \"pachytene checkpoint\" (reviewed in Ref. 303). An active checkpoint results in the phosphorylation and activation of protein kinase Mek1, which keeps its substrate Red1 phosphorylated (29, 102). When recombination has ended in late pachytene, the checkpoint is inactivated by the dephosphorylation of Red1 by PP1 (30). Overexpression of PP1 bypasses the checkpoint precociously. The nature of the regulatory subunit(s) associated with this meiotic function of PP1 remains unclear. A number of findings originally pointed to Gip1, a PP1- binding protein that is specifically expressed in middle meiosis and that is essential for sporulation (372). Thus it was reported that 1) Gip1 was required for the targetting of PP1 to chromosomes in late pachytene, 2) yeast cells lacking Gip1 displayed a pachytene arrest that was similar to that of cells with constitutively active Mek1 or with a deficient version of PP1, and 3) this arrest was alleviated by overexpression of PP1 (30). However, in a more recent study, deletion of the Gip1-encoding gene was found not to affect meiotic progression, but instead to interfere with the normal localization of sporulation-specific septins and the deposition of spore wall material (347). Strikingly, replacement of PP1 by a mutant version that fails to interact with Gip1 yielded a similar phenotype. IV. CELL CYCLE ARREST AND APOPTOSIS PP1 not only activates the Rb protein at the M/G1 transition (see sect. IIIC), but it is also implicated in the control of Rb at the G1/S transition and in Rb-mediated cell cycle arrest."

"Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation"

"GCIP, a newly identified cyclin D-interacting protein, was found to reduce the phosphorylation of retinoblastoma protein and inhibit E2F1-mediated transcriptional activity."

"We found that Id-1 expression induced phosphorylation of RB and down-regulation of p16(INK4a) but not p21(Waf1)or p27(Kip1)"

"PD 0183812 blocks phosphorylation on pRb in tumor cells PD 0183812 inhibits phosphorylation of pRb at serine 780"

"TGF-beta1 increased retinoblastoma protein phosphorylation at both Ser807/811 and Ser780. Silencing Nox4 prevented TGF-beta1-mediated retinoblastoma protein phosphorylation, proliferation, and cell hypertrophy. TGF-beta1 also increased phosphorylation of eukaryotic translation initiation factor 4E binding protein-1 at Thr37/46, and this was likewise blocked by silencing Nox4"

"TGF-beta1 increased retinoblastoma protein phosphorylation at both Ser807/811 and Ser780. Silencing Nox4 prevented TGF-beta1-mediated retinoblastoma protein phosphorylation, proliferation, and cell hypertrophy. TGF-beta1 also increased phosphorylation of eukaryotic translation initiation factor 4E binding protein-1 at Thr37/46, and this was likewise blocked by silencing Nox4"

"PD 0183812 blocks phosphorylation on pRb in tumor cells PD 0183812 inhibits phosphorylation of pRb at serine 780"

"TGF-beta1 increased retinoblastoma protein phosphorylation at both Ser807/811 and Ser780. Silencing Nox4 prevented TGF-beta1-mediated retinoblastoma protein phosphorylation, proliferation, and cell hypertrophy. TGF-beta1 also increased phosphorylation of eukaryotic translation initiation factor 4E binding protein-1 at Thr37/46, and this was likewise blocked by silencing Nox4"

"Rb was frequently phosphorylated at serine-807 and serine-811, and cyclin D1 was expressed in many of the tumors. Mutation of these serine residues prevented cyclin D-dependent phosphorylation from inactivating Rb in cultured cells. We conclude that Rb is frequently inactivated in uveal melanoma by phosphorylation of residues in the COOH-terminal region that regulate its activity, and one mechanism for this phosphorylation is overexpression of cyclin D. (Note that this causal statement is likely to be cell type non-specific)"

"Rb was frequently phosphorylated at serine-807 and serine-811, and cyclin D1 was expressed in many of the tumors. Mutation of these serine residues prevented cyclin D-dependent phosphorylation from inactivating Rb in cultured cells. We conclude that Rb is frequently inactivated in uveal melanoma by phosphorylation of residues in the COOH-terminal region that regulate its activity, and one mechanism for this phosphorylation is overexpression of cyclin D. (Note that this causal statement is likely to be cell type non-specific)."

"\"progression through G1 phase of cell cycle requires phosphorylation of the retinoblastoma gene product (pRb) by the cyclin D-dependent serine-threonine kinases CDK4 and CDK6"

"The phosphorylation levels of RB at serine residues 780 and 795 were decreased in LNCaP cells treated with androgens."

"TGF-beta1 increased retinoblastoma protein phosphorylation at both Ser807/811 and Ser780. Silencing Nox4 prevented TGF-beta1-mediated retinoblastoma protein phosphorylation, proliferation, and cell hypertrophy. TGF-beta1 also increased phosphorylation of eukaryotic translation initiation factor 4E binding protein-1 at Thr37/46, and this was likewise blocked by silencing Nox4"

"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"

"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"