Fig. 23.

The transcription-translation feedback loop in the CLOCK/NPAS2-BMAL1 and Per-Cry circadian clock system. NPAS2/CLOCK-BMAL1 heterodimer binding to the E-box region transactivates circadian clock proteins such as Period (Per), Cryptochrome (Cry), and other clock-controlled genes (CCGs). Per and Cry translocate to the cytosol and propagate the circadian rhythm cascade. Accumulated Per and Cry are either ubiquitinated or form heterodimers, which negatively regulate the function of NPAS2/CLOCK-BMAL1.