An essential role for chaperone-mediated autophagy in cell cycle progression

作者：Hubbi Maimon E; Semenza Gregg L^*

来源：Autophagy, 2015, 11(5): 850-851.

DOI：10.1080/15548627.2015.1037063

• chaperone-mediated autophagy
• cell cycle progression
• cyclin-dependent kinases
• DNA replication
• hypoxia-inducible factor

Hypoxia has long been known to serve as a stimulus for cell cycle arrest. Hypoxia-mediated cell cycle arrest is mediated through the actions of HIF1 (hypoxia inducible factor 1, subunit [basic helix-loop-helix transcription factor]), which has a nontranscriptional role as an inhibitor of MCM (minichromosome maintenance complex component) helicase activity. We identified chaperone-mediated autophagy as a pathway for selective degradation of HIF1 through lysosomes prior to the onset of DNA replication. CDK2 (cyclin-dependent kinase 2) mediates degradation of HIF1 at the G(1)/S transition, whereas CDK1 (cyclin-dependent kinase 1) increases HIF1 levels and transcriptional activity prior to the onset of G(1) phase. Lysosomal inhibitors induce cell cycle arrest, which is recovered by knockdown of HIF1 and EPAS1/HIF2. These findings establish lysosomes as essential regulators of cell cycle progression through the degradation of HIF1.

• 出版日期2015-5