Balance between DBT/CKIepsilon kinase and protein phosphatase activities regulate phosphorylation and stability of Drosophila CLOCK protein.

ABSTRACT: The first circadian-relevant kinase to be identified was DOUBLE-TIME (DBT) in Drosophila, a homolog of vertebrate CKIepsilon, which regulates the progressive phosphorylation and stability of PERIOD (PER) proteins in animals. A negative feedback loop wherein PER directly inhibits the transcriptional activity of the CLOCK-CYCLE (CLK-CYC) heterodimer is central to the generation of molecular rhythms and normal progression of the clock in Drosophila. We show that DBT activity is required for the phase-specific hyperphosphorylation of CLK in vivo, an event that correlates with times of maximal repression in per RNA levels. The ability of DBT to hyperphosphorylate CLK, enhance its degradation, and evoke modest inhibition of CLK-dependent transactivation from circadian promoter elements was direc

SUBMITTER: Kim EY 

PROVIDER: S-EPMC1458851 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature