Figure 1.

Diagrammatic description of the core circadian clock. The molecular clock is driven by transcriptional-translational feedback loops of the core clock genes and the oscillations of the clock-driven genes are regulated by transcriptional factors CLOCK/NPAS2 and BMAL1. The CLOCK/NPAS2 and BMAL1 heterodimerize and stimulate the expression of PER and CRY genes as well as ROR and REV-ERB genes by binding to an E-box region in their promoters. REV-ERB inhibits transcription of CLOCK/NPAS2 whilst ROR promotes Bmal1 expression. Additionally, PER is phosphorylated by CK1ε and degraded by proteasomes. Inhibition of CDK9 enhance REV-ERBα expression, thereby facilitating the liberation of REV-ERBα from CDK9. Molecules that inhibit or activate circadian core clock components in cancer are shown in black boxes.