CCND3

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene.

Full Name

Cyclin D3

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 G1/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 G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic 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 D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.

Biological Process

Cell division Source: UniProtKB-KW
Mitotic cell cycle phase transition Source: GO_Central
Negative regulation of transcription by RNA polymerase II Source: Ensembl
Positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
Positive regulation of G1/S transition of mitotic cell cycle Source: GO_Central
Positive regulation of protein phosphorylation Source: BHF-UCL
Regulation of cell population proliferation Source: Ensembl
Regulation of cyclin-dependent protein serine/threonine kinase activity Source: GO_Central
Regulation of insulin receptor signaling pathway Source: Ensembl
Signal transduction Source: Ensembl
T cell proliferation Source: Ensembl

Cellular Location

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

PTM

Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.