Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation.
GAPVD1
PER complex
circadian clock
protein degradation
protein phosphorylation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
06 Apr 2021
06 Apr 2021
Historique:
received:
24
03
2021
revised:
29
03
2021
accepted:
03
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
13
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33917494
pii: ijms22073787
doi: 10.3390/ijms22073787
pmc: PMC8038846
pii:
doi:
Substances chimiques
GAPVD1 protein, human
0
Guanine Nucleotide Exchange Factors
0
PER2 protein, human
0
Period Circadian Proteins
0
Casein Kinase Idelta
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : University Hospital Düsseldorf
ID : FoKo 2020-46
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