Circadian Clock Pathway
Transcription-translation feedback loops generating ~24-hour biological rhythms.
Overview
The mammalian circadian clock consists of interconnected transcription-translation feedback loops. CLOCK and BMAL1 heterodimerize and activate E-box-containing genes including Period (Per1/2/3) and Cryptochrome (Cry1/2). PER-CRY complexes accumulate, enter the nucleus, and repress CLOCK-BMAL1 activity, creating a ~24-hour oscillation. A secondary loop involves REV-ERBα/β and RORα/β/γ competing at RORE elements to regulate Bmal1 transcription. Post-translational modifications (phosphorylation by CK1δ/ε) fine-tune period length.
Cellular Location
SCN (master clock), peripheral tissues
Clinical Significance
Nobel Prize 2017 (Hall, Rosbash, Young); disruption linked to metabolic syndrome, cancer, and psychiatric disorders; chronotherapy optimizes drug timing; jet lag and shift work are circadian disruptions.