"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)."
"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."
"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."
"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]."
"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."
"We confirmed that CDK4 siRNA efficiently abolished p-Rb as well as CDK4 mRNA and protein expression (XREF_FIG)."
"The cyclin D1 and CDK4 complex inactivates Rb to promote G1/S transition and cell proliferation."
"CDK4 inhibits RB1, and CDKN2B inhibits CDK4 in the RB signaling pathway."
"Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression."
"The MDM2 gene product binds and inactivates p53 protein, whereas the CDK4 gene product is a cyclin dependent kinase and possibly inactivates Rb function."