Cyclin-Ds (CCNDs), the first cyclins (CCNs) to increase in the cell cycle, appears in mid G1 but is no longer detectable in the S phase. There are three forms of cyclin D, named D1 (CCND1), D2 (CCND2), and D3 (CCND3), but to simplify matters, we will use the general term "cyclin D."

Cyclin -Ds (CCNDs), like other cyclins (CCNs), are unstable and are degraded through the ubiquitin-proteasome pathway.

During the G1 phase of the cell cycle, CCNDs binds to and activates CDK4, forming a cyclin D-CDK4 complex. This D-CDK4 complex has a critical role in the cell cycle by phosphorylating the retinoblastoma susceptibility protein (RB).

The phosphorylation of RB is a molecular ON-OFF switch for the cell cycle. In its hypophosphorylated state, RB prevents cells from replicating by forming a tight, inactive complex with the transcription factor E2F. (E2F is a family of transcription factors, referred to here as "E2F.")

Phosphorylation of RB dissociates the complex and releases the inhibition on E2F transcriptional activity. Thus phosphorylation of RB eliminates the main barrier to cell-cycle progression and promotes cell replication.