The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-1α.
Biochemistry
Biological Sciences
Cell Biology
Molecular Biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
29 Mar 2019
29 Mar 2019
Historique:
received:
06
03
2018
revised:
03
01
2019
accepted:
22
02
2019
pubmed:
16
3
2019
medline:
16
3
2019
entrez:
16
3
2019
Statut:
ppublish
Résumé
The circadian clock and the hypoxia-signaling pathway are regulated by an integrated interplay of positive and negative feedback limbs that incorporate energy homeostasis and carcinogenesis. We show that the negative circadian regulator CRY1 is also a negative regulator of hypoxia-inducible factor (HIF). Mechanistically, CRY1 interacts with the basic-helix-loop-helix domain of HIF-1α via its tail region. Subsequently, CRY1 reduces HIF-1α half-life and binding of HIFs to target gene promoters. This appeared to be CRY1 specific because genetic disruption of CRY1, but not CRY2, affected the hypoxia response. Furthermore, CRY1 deficiency could induce cellular HIF levels, proliferation, and migration, which could be reversed by CRISPR/Cas9- or short hairpin RNA-mediated HIF knockout. Altogether, our study provides a mechanistic explanation for genetic association studies linking a disruption of the circadian clock with hypoxia-associated processes such as carcinogenesis.
Identifiants
pubmed: 30875610
pii: S2589-0042(19)30061-6
doi: 10.1016/j.isci.2019.02.027
pmc: PMC6416729
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
284-304Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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