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. Author manuscript; available in PMC: 2011 Mar 17.
Published in final edited form as: Annu Rev Physiol. 2010 Mar 17;72:605–624. doi: 10.1146/annurev-physiol-021909-135815

Figure 2.

Figure 2

The core molecular clock in Drosophila. CLOCK/CYCLE (CLK/CYC) bind to E-box elements (E) contained in the promoters of period ( per) and timeless (tim). PER and TIM proteins are modified by the kinases DOUBLETIME (DBT), CASEIN KINASE 2 (CK2), and SHAGGY (SGG) and the phosphatases PROTEIN PHOSPHATASE 2A (PP2A) and PROTEIN PHOSPHATASE 1 (PP1). PER and TIM dimerize and transition to the nucleus, where they repress CLK/CYC activity. Phosphorylated PER and TIM also bind the E3 ubiquitin ligase SUPERNUMERARY LIMBS (SLIMB), which leads to ubiquitination and ultimately proteolysis by the 26S proteasome.