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 journalArticle

47 Citations (Scopus)

Abstract

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
Volume18
Issue number7
DOIs
StatePublished - Apr 1 2004

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Cullin Proteins
Hydroxylation
Carcinogenesis
Homeostasis
Transcription Factors
Oxygen
Neoplasms
Hypoxia

Keywords

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

Cite this

Bemis, L., Chan, D. A., Finkielstein, C. V., Qi, L., Sutphin, P. D., Chen, X., ... Zundel, W. (2004). Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5. Genes and Development, 18(7), 739-744. https://doi.org/10.1101/gad.1180104

Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5. / Bemis, Lynne; Chan, Denise A.; Finkielstein, Carla V.; Qi, Lin; Sutphin, Patrick D.; Chen, Xiaojiang; Stenmark, Kurt; Giaccia, Amato J.; Zundel, Wayne.

In: Genes and Development, Vol. 18, No. 7, 01.04.2004, p. 739-744.

Research output: Contribution to journalArticle

Bemis, L, Chan, DA, Finkielstein, CV, Qi, L, Sutphin, PD, Chen, X, Stenmark, K, Giaccia, AJ & Zundel, W 2004, 'Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5', Genes and Development, vol. 18, no. 7, pp. 739-744. https://doi.org/10.1101/gad.1180104
Bemis L, Chan DA, Finkielstein CV, Qi L, Sutphin PD, Chen X et al. Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5. Genes and Development. 2004 Apr 1;18(7):739-744. https://doi.org/10.1101/gad.1180104
Bemis, Lynne ; Chan, Denise A. ; Finkielstein, Carla V. ; Qi, Lin ; Sutphin, Patrick D. ; Chen, Xiaojiang ; Stenmark, Kurt ; Giaccia, Amato J. ; Zundel, Wayne. / Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5. In: Genes and Development. 2004 ; Vol. 18, No. 7. pp. 739-744.
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