"CCND1, in association with cyclin dependent kinase (CDK4 and CDK6), phosphorylates the Rb, blocking its growth inhibitory activity, promoting cells to pass through the R point and thus driving them from G1 phase to S phase."
"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 )."
"DDT has also been shown to enhance proliferation by increasing the expression of Ccnd1 (cyclin D1)/E2f, inducing phosphorylation of pRb, increasing the expression of p53 degrading protein Mdm2 (a negative regulator of p53) and disrupting gap-junctional intercellular communication."
"These findings indicated that Cdk6 and Ccnd1 overexpression inhibited chondrocyte maturation and enhanced G1/S cell-cycle transition by phosphorylating pRb, but the chondrocytes failed to accomplish the cell cycle, and underwent p53 dependent apoptosis probably due to the dysregulation of E2f target genes."
"In addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected by CCND1 and CDK6 inactivating phosphorylation of RB1 at T356, inversely correlated with expression of EGFR in patient HNSCC samples."
"The primary substrates of CDK4/6 and CDK2 in G1 progression are the members of the retinoblastoma protein family RB,p107 and p130 The activity of the RB proteins is modulated by sequential phosphorylation by CDK4/6cyclinD and CDK2cyclinE complexes"
"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."