Cyclin D1 (PRAD1, Bcl-1) is a cytoplasmic and nuclear protein, which is synthesized during G1 phase and assembles with either cyclin-dependent kinase 4 (CDK4) or CDK6 in response to growth factor stimulation. D-type cyclin-CDK complexes act to inactivate the growth-suppressive function of the Rb protein through its phosphorylation, and titrate CDK inhibitors such as p21Cip1 and p27Kip1. Whereas during G1 phase cyclin D1 accumulates in the nucleus, it translocates into the cytoplasm during S phase. Without growth factor-mediated stimulation, cyclin D1 is unstable, and undergoes ubiquitin-mediated degradation, which is triggered by its phosphorylation. Cyclin D1 destabilization participates in G1/S phase arrest.
