IndraLab

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CDK4 inhibits RB1. 80 / 89
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"By contrast, assessment of the CDK4 and cyclin D1 complex and measurement of its kinase activity are entirely congruent with the proliferative response, and suggest that CDK4 compensated for diminished CDK2 activity to inactivate pRb and promote cell cycle progression (XREF_FIG)."
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"p16 blocks cell cycle progression by inhibiting the expression of CDK4/CDK6, which prevent the activation of pRB."
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"CDKN2B inhibits CDK4, CDK4 inhibits RB1."
32318558
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"Progression from G 1 to S relies on both Cdk4 and Cdk2 : Cdk4 and cyclin D is required to inactivate the Rb family of proteins at the restriction point, whereas Cdk2 and cyclin E is required not only [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18471976
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"Inhibition of CDK4 and CDK6 acts to restore the tumour suppressor role of Rb and promote cell cycle arrest."
30293995
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"According to the prevailing model, the major role of CDK4 and CDK6 is to inactivate pRB."
27033256
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"The effects of exogenous human telomerase reverse transcriptase expression, p53 knockdown, disruption of the pRb pathway by over-expression of CDK4 and reduced oxygen concentration on the lifespan of primary HCEC were evaluated."
22128747
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"Intuitively, any genomic alteration, including CDKN2A deletion, CDK4 amplification, and RB1 mutations, can inactivate RB, resulting in cell proliferation."
31815141
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"We also noticed that CDK4 siRNA transfection could abrogate the phosphorylated levels of downstream Rb molecule in CS-1 and SW1353 cells significantly."
30808351
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"p16 is a cyclin dependent kinase inhibitor of CDK4 and CDK6, which activates the negative cell cycle regulator retinoblastoma protein (pRB)."
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"CDK2 and CDK4 modulate cell cycle progression by inducing Rb dependent repression of E2F mediated transcription (XREF_FIG A and B)."
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"The pRB cell cycle regulatory cascade is frequently perturbed in neoplasia by overexpression of a component of the pRB phosphorylating cyclin D1 and CDK4 complex or by inactivation of pRB or the CDK4 inhibitors p16 and p15."
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"The cyclin D1-CDK4 complex inactivates Rb to promote G1/S transition and cell proliferation."
30519351
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"The authors suggest that one reason for this is the ability of deregulated cdk4 to fully inactivate pRb as a consequence of eroded phosphorylation site specificity in tumor cells."
12726855
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"The RB regulatory pathway is very commonly disrupted during tumorigenesis, by activation of cyclin D1 or Cdk4, or by elimination of the Cdk4 antagonist, p16, or RB itself."
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"Cyclin D1 and CDK4 phosphorylate and inactivate Rb during the G1/S transition, thereby allowing cell cycle progression to occur [6]."
26433123
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"CDK4 inhibition can induce Rb positive cells to exit the cell cycle into a non proliferative state, however, this can take the form of either quiescence, which is readily reversible, or senescence, which is more stable."
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"The mutually exclusive cyclin D1–Cdk4 and cyclin D2–Cdk4/6 pairing is able to inactivate the Rb protein, even in the presence of CKIs."
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"Aberrant cell cycle entry in post-mitotic neurons results in abnormal up-regulation of CDK4 that inactivates retinoblastoma protein (Rb) through phosphorylation resulting in activating E2 promoter-bin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29024678
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"Deletion of p18 (Ink4c) (p18), an inhibitor of CDK4 and CDK6, functionally inactivates the RB pathway, stimulates mammary luminal stem cell (LSC) proliferation, and leads to spontaneous luminal tumor development."
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"The combination of CDK4 and cyclin D1 can cause the retinoblastoma tumour suppressor (Rb) protein to lose its blocking effect on cell cycle by phosphorylating the Rb protein and realizing the effect of promoting and transforming the cell cycle (Pines, 1995)."
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"E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein (Annicotte et al, xref )."
20721988
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"These four genes are members of the RB signaling pathway (as annotated in xref ) involved in G1/S progression (by Bonferonni-corrected hypergeometric test): CDKN2A and CDKN2B inhibits CDK4, which in turn inhibits RB1."
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"Furthermore, Chou and collaborators showed that inhibition of CDK4 with palbociclib significantly induces apoptosis in pancreatic tumour overexpressing Rb and also enhances the apoptotic effect of chemotherapeutic gemcitabine in patient derived xenografts in mice."
30340359
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"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."
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"We confirmed that CDK4 siRNA efficiently abolished p-Rb as well as CDK4 mRNA and protein expression (XREF_FIG)."
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"CDK4 inactivates pRB and pRB may be required during OIS to induce a closed chromatin state that represses expression of genes that are required for cell proliferation ( xref )."
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"Cyclin D1 and cyclin dependent kinase-4 (CDK4) phosphorylate and inhibit RB to induce proliferation."
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"Cyclin D binds to CDK4, forming the active cyclin D–CDK4 complex, the cyclin D–CDK4 complex phosphorylates and inactivates the Rb."
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"Mechanistically, CDK4 phosphorylates and functionally inactivates the retinoblastoma (Rb) protein, which results in uninhibited cell cycle progression from G1 to S phase and restoring native cell cycle regulation by CDK4 inhibition could prevent uncontrolled proliferation."
29731991
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"CDK4 inhibits RB1, and CDKN2B inhibits CDK4 in the RB signaling pathway."
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"Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein."
20181095
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"The CKIs, p16, p15, p18 and p19, inhibit the activity of the CDKs CDK4 and CDK6, thereby preventing phopsphorylation of Rb, and G1 to S phase transition, and a mouse with a Cdk4 point mutation (Arg24Cys) that resulted in insensitivity to the CKIs, developed tumours of the pituitary, pancreas and testes."
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"During G1, Rb proteins are inactivated by sequential phosphorylation mediated by various Cdks, mainly the D-type cyclin dependent Cdk4 and Cdk6 and the E-type cyclin dependent Cdk2."
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"Levels of the cyclin-dependent kinase inhibitors (CDKIs) p18, p21 and p27 were shown to be increased in all treated RMS cell lines but no CDK4 inhibition or hypophosphorylation of the Rb protein suggesting that ATRA-induced differentiation was not sufficient to induce cell cycle arrest in RMS cells."
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"Cyclin D1 and Cdk4 complex inhibits Rb by partial phosphorylation, decreasing its association with E2F transcription factor and allowing E2F regulated activation of downstream gene transcription [XREF_BIBR, XREF_BIBR]."
26447757
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"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."
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"Cdk4 and Cdk2 can inactivate Rb family members, including p107, by phosphorylation."
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"Cyclin D1 and CDK4 phosphorylate and inactivate Rb during the G1/S transition, thereby allowing cell cycle progression to occur [XREF_BIBR]."
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"We used a panel of DLBCL cell lines derived from patients with relapsed and refractory disease; all lines have decreased or absent p53 activity and CNAs of cell cycle components including CDKN2A, CCND3, CDK4, CDK6, CDK2 and/or copy loss of RB1 (XREF_SUPPLEMENTARY)."
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"In complexes with D-type cyclins, the cyclin-dependent kinase-4 (CDK4) phosphorylates and inactivates RB1 [ xref , xref ]."
29963241
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"Rb negative tumors were expected to be resistant to abemaciclib treatment, since CDK4 and 6 inhibitors inhibit upstream of Rb; however, abemaciclib effects were not associated with Rb expression status."
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"To investigate the requirement for p53 and Rb activity in senescence-associated OPN regulation, we ectopically expressed a well-characterized dominant negative p53 cDNA (p53-DD) ( xref ) or a cDNA expressing a fusion protein consisting of a mutant form of cyclin dependent kinase 4 R24C (Cdk4) and cyclin D1 (DK) that inhibits Rb ( xref ) ( xref )."
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"Palbociclib, an inhibitor of CDK4 and CDK6, restores cell cycle checkpoints independently of Rb."
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"CDKN2A inhibits CDK4 and CDK4 inhibits RB1 in the RB signaling pathway."
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"Intriguingly, the knockdown of both CDK4 and CDK6, but not CDK2, allowed RB to become the most hypophosphorylated form and converted the SN38 sensitive cells to a resistant state."
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"CDK4 and 6 negatively regulate Rb activity through phosphorylation and inactivation of this tumor suppressor protein; therefore, it is possible that only tumors containing Rb-proficient cells may be sensitive to CDK4 and 6 inhibition."
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"In particular a high fraction of tumors exhibit amplification of the p53 negative regulators MDM2, 4 and WIP1, as well as CDK4 which negatively regulates Rb."
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"Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4 dependent inactivation of the pRB protein."
20181095
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"Cyclin D1 and CDK4 phosphorylate and inactivate Rb during the G1/S transition, thereby allowing cell cycle progression to occur [ xref ]."
21437219
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"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."
15809340
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"p14 ARF mediates growth arrest by stabilizing the tumor suppressor p53 [ xref ], whereas p16 induces cellular senescence by preventing the inactivation of the retinoblastoma protein (pRB) by the cyclin dependent kinases cdk4 and cdk6 [ xref , xref ], a step otherwise required for cell cycle progression."
27029014
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"CDK4 and its close homolog CDK6 form heterodimers with D-type cyclins, and CDK4/6-mediated deactivation of the retinoblastoma (RB) tumor suppressor is critical for cell-cycle progression [40]."
33885378
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"Cyclin D1 and Cdk4 complex inhibits Rb by appropriate phosphorylation andreduces its association with E2F transcription factor, leading tothe activation of downstream gene transcription [XREF_BIBR]."
27769069
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"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."
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"The resulting cyclin D1-CDK4 complex inhibits retinoblastoma protein, thus facilitating the transcription of S-phase genes [ xref ]."
31717401
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"Furthermore, the p16 INK4a -driven inhibition of CDK4 and CDK6 promotes changes in cell morphology independent of Rb, suggesting additional kinase targets may contribute to the activity of p16 INK4a."
18843795
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"The cyclin D1 and CDK4 complex inactivates Rb to promote G1/S transition and cell proliferation."
30519351
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"CDK4 inhibits RB1, and CDKN2B inhibits CDK4 in the RB signaling pathway."
25859819
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"The MDM2 gene product binds and inactivates p53 protein, whereas the CDK4 gene product is a cyclin dependent kinase and possibly inactivates Rb function."
18782081
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"These results are consistent with a model in which the only requirement of cdk4 in MCF-7 cell proliferation is to inactivate pRb family members XREF_BIBR, XREF_BIBR."
18060053
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"Subsequent studies have demonstrated that overexpression of cyclin D1 or cdk4, instead of HPV E6/E7, effectively inhibited Rb activity and might be an alternative method of overcoming premature senescence in primary epithelial cells of other origins."
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"The activities of cyclin dependent kinase 2 (Cdk2) and cyclin dependent kinase 4 (Cdk4) are greatly reduced, due mostly to the increased expression of the Cdk inhibitor (CKI) proteins p21 CIP1 and WAF[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Thus, the dual role of Rb in regulating cell proliferation and differentiation is mediated by its phosphorylation status. xref Both cyclin D1-CDK4 and cyclin E-CDK2 phosphorylate Rb during the G1/S cell cycle progression, and cyclin D1-CDK4 specifically phosphorylates Rb at Serine 780 in vitro in human fibroblasts. xref We previously reported that sepsis inhibits cyclin-dependent kinase inhibitor p21 expression due to increases in the NFI-A protein. xref P21 inhibits the cyclin D1-CDK4 protein complex, which facilitates cell cycle arrest and promotes cell differentiation. xref , xref In this study, knockdown of cyclin D1 or CDK4 in sepsis Gr1 + CD11b + cells inhibited Rb phosphorylation at Serine 780 ( xref ), Rb knockdown displaced C/EBPβ from the miR promoters and simultaneously induced C/EBPα binding ( xref ) and abolished the miR promoter-driven reporter gene expression ( xref )."
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"Rb itself is inactivated through phosphorylation by the Cyclin D1 and CDK4 complex, liberating E2F to promote cell entry into S phase."
26834515
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"Nevertheless, in our follow-up experiments, we recapitulated the CDK4-RB interaction as RB (phosphorylated at Ser 780 and Ser 807) was suppressed by PD0332991 and by CDK4 directed siRNA (XREF_FIG)."
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"Cyclin D1/D3 promote CDK4 and CDK6 activities that stabilize the anti-senescence transcription factor FoxM1 and inhibit Rb, causing Rb release from E2F transcription factors that drive cell cycle progression (XREF_FIG)."
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"Cycle inhibitory proteins p15 INK4b and p16 INK4a encoded by this locus are able to induce cell cycle arrest in G1 by inhibiting cyclin dependent kinases CDK4 and CDK6 which normally inactivate two tumour-suppressor pathways, Rb and p53."
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"The activities of cyclin dependent kinase 2 (Cdk2) and cyclin dependent kinase 4 (Cdk4) are greatly reduced, due to the increased expression of the Cdk inhibitor proteins p21, and p16, causing Rb to be present in its hypophosphorylated form."
18852884
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"CDKN2A inhibits CDK4 and CDK4 inhibits RB1 in the RB signaling pathway."
25859819
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"Further reinforcing this notion were experiments utilizing supra-physiologic overexpression of D-type cyclins and Cdk4 and Cdk6 that inactivated Rb and drove cells into S phase."
24876129
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"In particular a high fraction of tumors exhibit amplification of the p53 negative regulators MDM2, 4 and WIP1, and CDK4 which is also known to negatively regulate Rb."
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"Cyclin D1 and CDK4 phosphorylate and inactivate Rb during the G1/S transition, thereby allowing cell cycle progression to occur [6] ."
26433123
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"Since CDK4-dependent Rb inactivation contributes to subsequent CDK2 activation in late G 1 (due to induction of cyclins E and A), we also determined the effect of Mcm7-depletion on CDK2 activity."
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"During the G 1 phase, Rb proteins are inactivated by sequential phosphorylation mediated by various Cdks, mainly the D-type cyclin dependent Cdk4 and Cdk6 and the E-type cyclin dependent Cdk2."
22450747
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"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."
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"These four genes are members of the RB signaling pathway involved in G1/S progression (by Bonferonni corrected hypergeometric test) : CDKN2A and CDKN2B inhibits CDK4, which in turn inhibits RB1."
23717195
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"PRb, which controls the G1-S checkpoint of the cell cycle, was inhibited by the CCND1-CDK4 complex in the promotion of passage via the G1 phase."
29488616
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"E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4 dependent inactivation of the pRB protein."
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"Despite the traditional association of senescence with the G0 phase, one known mechanism of senescence begins with the tumor suppressor p16 Ink4a (CDKN2A), which inhibits Rb inactivation by CDK4 and CDK6, leading to failure to transition from G1 phase into S phase [ xref , xref ]."
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