Fig. 1
From: CDK4/6 inhibitors: a novel strategy for tumor radiosensitization
Physiological functions and regulation of the cyclin D-CDK4/6 complex. Cyclin D-CDK4/6 complex facilitates G1-S transition. In the early G1 phase, mitogenic signals stimulate the accumulation of D-type cyclins and induce the formation of the cyclin D-CDK4/6 complex, which phosphorylates RB. Once hypophosphorylated, RB is prepared for hyperphosphorylation by the increased levels of the cyclin E-CDK2 complex. The transcription factor E2F is released from the RB-E2F complex due to the lack of the inhibitory effects of RB, enabling cells to proceed into S phase. Cyclin D-CDK4/6 activity is also regulated by mTORC1 and Ink4 family proteins. The PI3K and RAS pathway phosphorylate TSC2 to enhance mTORC1 activity, thus increasing cyclin D1 levels. Conversely, Ink4 family proteins inactivate the kinase to block cell cycle progression