Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.
Rudolf Buchheim Institute of Pharmacology, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.
Cell Death Dis. 2023 Jul 27;14(7):477. doi: 10.1038/s41419-023-06012-7.
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.
缺氧诱导因子（HIF）家族被激活以适应细胞在低氧条件下的生存，但也已知其在常氧条件下调节某些生物学过程。在这里，我们显示 HIF-1α 蛋白水平在细胞周期的 G1 期（称为 G1-HIF）中以 AMP 激活的蛋白激酶（AMPK）依赖性方式短暂增加。通过去稳定系统瞬时消除 G1-HIF 揭示了其在不利代谢条件下对细胞存活的贡献。事实上，G1-HIF 在细胞周期依赖性表达编码代谢调节剂的基因和在营养剥夺条件下维持 mTOR 活性中发挥关键作用。因此，瞬时消除 G1-HIF 导致关键蛋白质氨基酸和碳水化合物浓度的显著降低。这些数据表明，G1-HIF 作为细胞周期依赖性监测因子发挥作用，可防止饥饿诱导的细胞凋亡的发生。
