Science and Research

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

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.

  • Belapurkar, R.
  • Pfisterer, M.
  • Dreute, J.
  • Werner, S.
  • Zukunft, S.
  • Fleming, I.
  • Kracht, M.
  • Schmitz, M. L.

Keywords

  • Cell Survival/genetics
  • G1 Phase
  • *Apoptosis/genetics
  • Cell Cycle/genetics
  • *Hypoxia-Inducible Factor 1, alpha Subunit/genetics
  • Cell Hypoxia/physiology
Publication details
DOI: 10.1038/s41419-023-06012-7
Journal: Cell Death Dis
Pages: 477 
Number: 7
Work Type: Original
Location: UGMLC
Disease Area: General Lung and Other
Partner / Member: JLU
Access-Number: 37500648

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