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Citation
Yu, W., Zheng, H., Price, J.L., Hardin, P.E. (2009). DOUBLETIME plays a noncatalytic role to mediate CLOCK phosphorylation and repress CLOCK-dependent transcription within the Drosophila circadian clock.  Mol. Cell. Biol. 29(6): 1452--1458.
FlyBase ID
FBrf0207013
Publication Type
Research paper
Abstract

Circadian clocks keep time via gene expression feedback loops that are controlled by time-of-day-specific changes in the synthesis, activity, and degradation of transcription factors. Within the Drosophila melanogaster circadian clock, DOUBLETIME (DBT) kinase is necessary for the phosphorylation of PERIOD (PER), a transcriptional repressor, and CLOCK (CLK), a transcriptional activator, as CLK-dependent transcription is being repressed. PER- and DBT-containing protein complexes feed back to repress CLK-dependent transcription, but how DBT promotes PER and CLK phosphorylation and how PER and CLK phosphorylation contributes to transcriptional repression have not been defined. Here, we show that DBT catalytic activity is not required for CLK phosphorylation or transcriptional repression and that PER phosphorylation is dispensable for repressing CLK-dependent transcription. These results support a model in which DBT plays a novel noncatalytic role in recruiting additional kinases that phosphorylate CLK, thereby repressing transcription. A similar mechanism likely operates in mammals, given the conserved activities of PER, DBT, and CLK orthologs.

PubMed ID
PubMed Central ID
PMC2648245 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Cell. Biol.
    Title
    Molecular and Cellular Biology
    Publication Year
    1981-
    ISBN/ISSN
    0270-7306
    Data From Reference
    Alleles (6)
    Genes (7)
    Physical Interactions (3)
    Natural transposons (1)
    Insertions (2)
    Transgenic Constructs (3)