G1/S-specific cyclin-D3 phospho T283
Function
Regulatory component of the cyclin D3-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 (PubMed:8114739). 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 (PubMed:8114739). Hypophosphorylates RB1 in early G(1) phase (PubMed:8114739). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:8114739). Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:16782892). Shows transcriptional coactivator activity with ATF5 independently of CDK4 (PubMed:15358120).
Post-translational modifications
Phosphorylation at Thr-283 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.
Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-283 phosphorylation (PubMed:33854235, PubMed:33854239). The DCX(AMBRA1) complex represents the major regulator of CCND3 stability during the G1/S transition (PubMed:33854235, PubMed:33854239). Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation (PubMed:22020328).
Sequence Similarities
Belongs to the cyclin family. Cyclin D subfamily.
Cellular localization
- Nucleus
- Cytoplasm
Alternative names
G1/S-specific cyclin-D3, CCND3