FIGURE 3.

The cross-talk between the cell cycle and the circadian rhythm. The cross-talk between the cell cycle and the circadian rhythm can occur via three major molecular mechanisms. Firstly, mitosis inhibitor protein kinase WEE1 regulates the G2/M transition by phosphorylating the amino acids of Cdk1 thereby inhibiting the kinase activity and preventing entry into mitosis. Wee1 gene promoter consists of CLOCK/BMAL1 responsive E-box elements that control the expression of WEE1 in a circadian manner. Secondly, the transition of the G1 to S phase is under the circadian control ROR/REV-ERB pathway by targeting the p21Waf1/CIP1 a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle progression. Thirdly, the phosphorylation of REV-ERBα via CDK1 targets this clock transcription inhibitory component for ubiquitination and degradation by the F-box protein FBXW7. Abbreviations: BMAL1, Bone Muscle Arnt-like protein 1; CDK1, Cyclin-dependent kinase 1; CLOCK, Circadian Locomotor Output Cycles Kaput; E-box, Enhancer box; F/box/FBXW7, F-Box And WD Repeat Domain Containing 7; G1 phase, Gap1 phase; G2/M transition, Gap2/Mitosis transition; p21Waf1/CIP1, Cyclin-dependent kinase inhibitor 1; REV-ERBα, nuclear receptor subfamily 1, group D, member 1; ROR, Retinoic acid receptor-related Orphan Receptor; S phase, Synthetic phase.