Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation
| Autor: | Hussam Ibrahim, Faiza Kalfalah, Anna-Lena Grothoff, Hans Reinke, Valerie Rudenko, Anja Stefanski, Christina Buschhaus, Niklas Berleth, Kai Stühler, Philipp Reus, Anna Katharina Mundorf, Björn Stork |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Period (gene)
Circadian clock Repressor Protein degradation Article Catalysis lcsh:Chemistry Inorganic Chemistry Circadian Clocks circadian clock PER complex Guanine Nucleotide Exchange Factors Humans Protein phosphorylation Phosphorylation Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Spectroscopy Chemistry Organic Chemistry Period Circadian Proteins General Medicine GAPVD1 protein phosphorylation Computer Science Applications Cell biology PER2 lcsh:Biology (General) lcsh:QD1-999 CSNK1D Casein Kinase Idelta Proteolysis protein degradation HeLa Cells |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 3787, p 3787 (2021) International Journal of Molecular Sciences Volume 22 Issue 7 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22073787 |
| Popis: | Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock. |
| Databáze: | OpenAIRE |
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