Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Hypo phosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenomic and antimitogenic signals.

Cellular Localization

Nucleus. Cytoplasm Nucleus membrane. Note=Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members

Function

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition . Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase . Hypo phosphorylates RB1 in early G(1) phase . Cyclin D-CDK4 complexes are major integrators of various mitogenomic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner .