SIRT1 deacetylates and stabilizes hypoxia-inducible factor-1α (HIF-1α) via direct interactions during hypoxia

Hyun Yoo Joo, Miyong Yun, Jaemin Jeong, Eun Ran Park, Hyun Jin Shin, Seon Rang Woo, Jin Kyu Jung, Yong Min Kim, Joong Jean Park, Joon Kim, Kee Ho Lee

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


Abstract Upon shift to a hypoxic environment, cellular HIF-1α protein is stabilized, with a rapid decline in oxygen-sensitive hydroxylation. Several additional post-translational modifications of HIF-1α are critical in controlling protein stability during hypoxia. In the present study, we showed that SIRT1 stabilizes HIF-1α via direct binding and deacetylation during hypoxia. SIRT1 depletion or inactivation led to reduced hypoxic HIF-1α accumulation, accompanied by an increase in HIF-1α acetylation. Impaired HIF-1α accumulation was recovered upon inhibition of 26S proteasome activity, indicating that SIRT1 is essential for HIF-1α stabilization during hypoxia. Consistently, HIF-1α accumulation was enhanced upon overexpression of wild-type SIRT1, but not its dominant-negative form. SIRT1-mediated accumulation of HIF-1α protein led to increased expression of HIF-1α target genes, including VEGF, GLUT1 and MMP2, and ultimate promotion of cancer cell invasion. These findings collectively imply that hypoxic HIF-1α stabilization requires SIRT1 activation. Furthermore, SIRT1 protection of HIF-1α from acetylation may be a prerequisite for stabilization and consequent enhancement of cell invasion.

Original languageEnglish
Article number33865
Pages (from-to)294-300
Number of pages7
JournalBiochemical and biophysical research communications
Issue number4
Publication statusPublished - 2015 Jun 12

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea ( NRF-2012R1A1A2008457 , NRF-2012M3A9B6055346 , NRF-2014M3A9A8064818 and NRF-2012R1A2A1A01009027) and National Nuclear R&D program of the Ministry of Science and Technology .

Publisher Copyright:
© 2015 Elsevier Inc.


  • Deacetylation
  • HIF-1α
  • Interaction
  • Invasion
  • SIRT1
  • Stabilization

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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