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Genes Dev. 2021 Aug 01;35(15):1161-1174. doi: 10.1101/gad.348622.121. Epub 2021 Jul 22.

Protein phosphatase 4 controls circadian clock dynamics by modulating CLOCK/BMAL1 activity.

Genes & development

Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C Fiorenza, Irem Kaymak, Anna K Fritzsche, Erik D Herzog, Ralf Stanewsky, Achim Kramer

Affiliations

  1. Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin,10117 Berlin, Germany.
  2. Institute of Neuro and Behavioral Biology, Westfälische Wilhelms University, Münster 48149, Germany.
  3. Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA.

PMID: 34301769 PMCID: PMC8336894 DOI: 10.1101/gad.348622.121

Abstract

In all organisms with circadian clocks, post-translational modifications of clock proteins control the dynamics of circadian rhythms, with phosphorylation playing a dominant role. All major clock proteins are highly phosphorylated, and many kinases have been described to be responsible. In contrast, it is largely unclear whether and to what extent their counterparts, the phosphatases, play an equally crucial role. To investigate this, we performed a systematic RNAi screen in human cells and identified protein phosphatase 4 (PPP4) with its regulatory subunit PPP4R2 as critical components of the circadian system in both mammals and

© 2021 Klemz et al.; Published by Cold Spring Harbor Laboratory Press.

Keywords: BMAL1; CLOCK; circadian clock; circadian rhythm; phosphorylation; protein phosphatase 4

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