Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5

Lynne Bemis, Denise A. Chan, Carla V. Finkielstein, Lin Qi, Patrick D. Sutphin, Xiaojiang Chen, Kurt Stenmark, Amato J. Giaccia, Wayne Zundel

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Mammalian oxygen homeostasis is dependent on the HIF family of transcription factors. The CSN subunit, CSN5, binds both the CODD of HIF-1α and the pVHL tumor suppressor. High CSN5 expression generates a pVHL-independent form of CSN5 that stabilizes HIF-1α aerobically by inhibiting HIF-1α prolyl-564 hydroxylation. Aerobic CSN5 association with HIF-1α occurs independently of the CSN holocomplex, leading to HIF-1α stabilization independent of Cullin 2 deneddylation. CSN5 weakly associates with HIF-1α under hypoxia, but is required for optimal hypoxia-mediated HIF-1α stabilization. These results indicate that CSN5 regulates aerobic as well as hypoxic HIF-1α stability by different mechanisms during oncogenesis.

Original languageEnglish (US)
Pages (from-to)739-744
Number of pages6
JournalGenes and Development
Issue number7
StatePublished - Apr 1 2004


  • COP9 signalosome
  • Hypoxia inducible factor-1α
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5'. Together they form a unique fingerprint.

Cite this