Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse

Figure 4

The molecular clocks of Drosophila (a) and mammals (b). (a) In Drosophila, dCLK and CYC form a dimer, which binds to the E boxes in the promoter of per and tim as well as to other clock-controlled genes to facilitate transcription. PER and TIM proteins form a complex and translocate into the nucleus providing negative feedback to inhibit dCLK-CYC DNA binding. Phosphorylation mediated by DBT and SGG regulates protein–protein interactions, nuclear translocation, and degradation. (b) In mammals, the transcription factors BMAL1 and CLK form a dimer that binds to E boxes in the promoter of mPer and mCry. mPER and mCRY proteins form dimers, enter the nucleus, and inhibit the BMAL1-CLK activity. Phosphorylation mediated by CK1 and GSK3 regulates protein–protein interactions, nuclear translocation, and degradation.

(a)

(b)