Journal
CELL REPORTS
Volume 11, Issue 8, Pages 1266-1279Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.04.033
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Funding
- Agence Nationale de la Recherche DrosoClock
- Agence Nationale de la Recherche ClockGene
- Agence Nationale de la Recherche Fun-GenDroso
- Equipe FRM program of Fondation pour la Recherche Medicale
- European Union
- Ministere de l'Enseignement Superieur et de la Recherche
- Institut National de la Sante et des Etudes et Recherches Medicales
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In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates transcription of period (per) and timeless (tim) in the evening. PER and TIM proteins then repress CLOCK (CLK) activity during the night. The pace of the oscillator depends upon post-translational regulation that affects both positive and negative components of the transcriptional loop. CLK protein is highly phosphorylated and inactive in the morning, whereas hypophosphorylated active forms are present in the evening. How this critical dephosphorylation step is mediated is unclear. We show here that two components of the STRIPAK complex, the CKA regulatory subunit of the PP2A phosphatase and its interacting protein STRIP, promote CLK dephosphorylation during the daytime. In contrast, the WDB regulatory PP2A subunit stabilizes CLK without affecting its phosphorylation state. Inhibition of the PP2A catalytic subunit and CKA downregulation affect daytime CLK similarly, suggesting that STRIPAK complexes are the main PP2A players in producing transcriptionally active hypophosphorylated CLK.
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