Figure 2.

Post-translational modifications in the circadian clock. The current understanding for post-translational regulation of the circadian clock is modeled. A) Clock and Bmal1 dimerize and transcriptionally activate clock-controlled genes, including Per and Cry. B) Per and Cry interact in the cytosol. C) Per is phosphorylated by CK1δ/ε, causing it to translocate into the nucleus. D) Per and Cry repress Clock and Bmal1 activity. E) Phosphorylated Per1 is potentially dephosphorylated by protein phosphatase 1 (PP1), either in the cytosol or in the nucleus (causing nuclear export). P, phosphorylation. Dotted lines indicate hypothetical mechanisms.