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

Maimon E. Hubbi, Gregg L. Semenza

Research output: Contribution to journalArticle

Abstract

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 HIF1α (hypoxia inducible factor 1, α 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 HIF1α through lysosomes prior to the onset of DNA replication. CDK2 (cyclin-dependent kinase 2) mediates degradation of HIF1α at the G1/S transition, whereas CDK1 (cyclin-dependent kinase 1) increases HIF1α levels and transcriptional activity prior to the onset of G1 phase. Lysosomal inhibitors induce cell cycle arrest, which is recovered by knockdown ofHIF1a and EPAS1/HIF2α. These findings establish lysosomes as essential regulators of cell cycle progression through the degradation of HIF1α.

Original languageEnglish (US)
Pages (from-to)850-851
Number of pages2
JournalAutophagy
Volume11
Issue number5
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cell cycle progression
  • Chaperone-mediated autophagy
  • Cyclin-dependent kinases
  • DNA replication
  • Hypoxiainducible factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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