G1-S细胞周期信号通路图  (点击信号分子查询相关抗体)

Cyclin Ds are upregulated in response to Ras-Map kinase signalling and assembled with cyclin D-dependent kinases (CDKs). The CDKs initiate Rb phosphorylation, releasing E2F from negative constraints and facilitating activation of a series of E2F-responsive genes, the products of which are necessary for S-phase entry. Activation of cyclin E by E2F enables formation of the cyclin E-cdk2 complex. This is accelerated by the continued sequestration of Cip/Kip proteins into complexes with assembling cyclin D-cdk complexes. Cyclin E-cdk2 completes the phosphorylation of Rb, further enabling activation of E2F-responsive genes, including cyclin A. Cyclin E-Cdk2 also stimulates DNA synthesis presumably by facilitating origin firing through Cdc45-dependent loading of DNA polymerase and promoting histone biosynthesis through direct phosphorylation of NPAT, a factor required for histone transcription. (Contributed by Dr. Koji Nakade)