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Institute of Pharmacology and Toxicology Chronobiology and Sleep Research

The Mammalian Circadian Oscillator

Model of the mammalian circadian clock mechanism

From Albrecht, U., and Eichele, G. (2003). The mammalian circadian clock. Curr Opin Genet Dev 13, 271-277.

CLOCK (yellow) and BMAL1 (purple) proteins (positive limb) heterodimerize and drive the expression of Per, Cry and Rev-erbα genes in the nucleus. PER (red) and CRY (light green) proteins interact in the nucleus to inhibit CLOCK/BMAL1 action by a yet unknown mechanism and thereby down-regulate their own expression and that of Rev-erbα (dark green). When REV-ERBα protein is absent, Bmal1 is derepressed and hence transcribed to produce new CLOCK/BMAL1 transcription factors that reinitiate a new circadian cycle. Clock proteins are posttranslationally modified; casein kinase I (CKI), for example, phosphorylates PER2. Hyperphosphorylation of PER2 promotes its degradation.