A transient increase of HIF-1α during the G1 phase (G1-HIF) ensures cell survival under nutritional stress.


Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
27 07 2023
Historique:
received: 25 01 2023
accepted: 17 07 2023
revised: 11 07 2023
medline: 31 7 2023
pubmed: 28 7 2023
entrez: 27 7 2023
Statut: epublish

Résumé

The family of hypoxia-inducible transcription factors (HIF) is activated to adapt cells to low oxygen conditions, but is also known to regulate some biological processes under normoxic conditions. Here we show that HIF-1α protein levels transiently increase during the G1 phase of the cell cycle (designated as G1-HIF) in an AMP-activated protein kinase (AMPK)-dependent manner. The transient elimination of G1-HIF by a degron system revealed its contribution to cell survival under unfavorable metabolic conditions. Indeed, G1-HIF plays a key role in the cell cycle-dependent expression of genes encoding metabolic regulators and the maintenance of mTOR activity under conditions of nutrient deprivation. Accordingly, transient elimination of G1-HIF led to a significant reduction in the concentration of key proteinogenic amino acids and carbohydrates. These data indicate that G1-HIF acts as a cell cycle-dependent surveillance factor that prevents the onset of starvation-induced apoptosis.

Identifiants

pubmed: 37500648
doi: 10.1038/s41419-023-06012-7
pii: 10.1038/s41419-023-06012-7
pmc: PMC10374543
doi:

Substances chimiques

Hypoxia-Inducible Factor 1, alpha Subunit 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

477

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ratnal Belapurkar (R)

Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.

Maximilian Pfisterer (M)

Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.

Jan Dreute (J)

Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.

Sebastian Werner (S)

Rudolf Buchheim Institute of Pharmacology, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.

Sven Zukunft (S)

Institute for Vascular Signalling, Goethe University, Frankfurt am Main, Germany.

Ingrid Fleming (I)

Institute for Vascular Signalling, Goethe University, Frankfurt am Main, Germany.
German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany.

Michael Kracht (M)

Rudolf Buchheim Institute of Pharmacology, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.

M Lienhard Schmitz (ML)

Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany. lienhard.schmitz@biochemie.med.uni-giessen.de.

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Classifications MeSH