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Cell Rep. 2015 May 26;11(8):1266-79. doi: 10.1016/j.celrep.2015.04.033. Epub 2015 May 14.

Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila.

Author information

1
Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
2
Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, 91190 Gif-sur-Yvette, France.
3
Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France. Electronic address: rouyer@inaf.cnrs-gif.fr.

Abstract

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.

PMID:
25981041
DOI:
10.1016/j.celrep.2015.04.033
[Indexed for MEDLINE]
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