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

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 (min...

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Bibliographic Details
Published in:Autophagy 2015-01, Vol.11 (5), p.850-851
Main Authors: Hubbi, Maimon E, Semenza, Gregg L
Format: Article
Language:English
Subjects:
Autophagic Punctum
Autophagy
CDK, cyclin-dependent kinase
Cell Cycle
cell cycle progression
chaperone-mediated autophagy
cyclin-dependent kinases
DNA replication
HIF, hypoxia-inducible factor
Humans
hypoxia-inducible factor
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
MCM, minichromosome maintenance complex component
Models, Biological
Molecular Chaperones - metabolism
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Summary: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 G 1 /S transition, whereas CDK1 (cyclin-dependent kinase 1) increases HIF1α levels and transcriptional activity prior to the onset of G 1 phase. Lysosomal inhibitors induce cell cycle arrest, which is recovered by knockdown of HIF1α and EPAS1/HIF2α. These findings establish lysosomes as essential regulators of cell cycle progression through the degradation of HIF1α.
ISSN:1554-8627
1554-8635
DOI:10.1080/15548627.2015.1037063