Which cyclin accumulates in S phase to promote DNA replication?
Orderly appearance and destruction of cyclins dictates CDK activation windows. Mitogenic stimulation through receptor tyrosine kinases activates Ras-MAPK cascade leading to transcription factor AP-1, Myc, and beta-catenin mediated induction of cyclin D1, D2, D3 genes. Cyclin D proteins accumulate throughout G1, assembling with CDK4 and CDK6 kinases whose activity requires mitogen-dependent stabilization and CAK phosphorylation. Cyclin D-CDK4/6 complexes phosphorylate retinoblastoma proteins at early sites, initiating limited E2F release and transcription of cyclin E. Cyclin E-CDK2 then complet
Ref: Bertoli et al., Nature Reviews Mol Cell Biol 2013, Cyclin Control. Alberts 7th ed., Chapter 17.