Protein interaction networks of the mammalian core clock proteins.

Circadian rhythm is a 24-h cycle that regulates the biochemical and behavioral changes of organisms. It controls a wide range of functions, from gene expression to behavior, allowing organisms to anticipate daily changes in their environment. In mammals, circadian rhythm is generated by a complex transcriptional and translational feedback loop mechanism. The binding of CLOCK/BMAL1 heterodimer to the E-box of DNA located within the promoter region initiates transcription of clock control genes including the transcription of the other two core clock genes of Periods (Pers) and Cryptochromes (Crys). Then PERs and CRYs along with casein kinase 1ɛ/Δ translocate into the nucleus where they suppress CLOCK/BMAL1 transactivation and, in turn, clock-regulated gene expression. Various clock components must be operational to aid in their stabilization and period extension in circadian rhythm. In this review, we have highlighted the recent progress for the core clock interacting proteins to maintain and to stabilize circadian rhythm in mammals.