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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. © 2023. The Author(s).


Ratnal Belapurkar, Maximilian Pfisterer, Jan Dreute, Sebastian Werner, Sven Zukunft, Ingrid Fleming, Michael Kracht, M Lienhard Schmitz. A transient increase of HIF-1α during the G1 phase (G1-HIF) ensures cell survival under nutritional stress. Cell death & disease. 2023 Jul 27;14(7):477

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PMID: 37500648

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