Regulation of cell proliferation by hypoxia-inducible factors

Maimon E. Hubbi, Gregg L. Semenza

Research output: Contribution to journalReview articlepeer-review

110 Scopus citations


Hypoxia is a physiological cue that impacts diverse physiological processes, including energy metabolism, autophagy, cell motility, angiogenesis, and erythropoiesis. One of the key cell-autonomous effects of hypoxia is as a modulator of cell proliferation. For most cell types, hypoxia induces decreased cell proliferation, since an increased number of cells, with a consequent increase in O2 demand, would only exacerbate hypoxic stress. However, certain cell populations maintain cell proliferation in the face of hypoxia. This is a common pathological hallmark of cancers, but can also serve a physiological function, as in the maintenance of stem cell populations that reside in a hypoxic niche. This review will discuss major molecular mechanisms by which hypoxia regulates cell proliferation in different cell populations, with a particular focus on the role of hypoxia-inducible factors.

Original languageEnglish (US)
Pages (from-to)C775-C782
JournalAmerican Journal of Physiology - Cell Physiology
Issue number12
StatePublished - Dec 15 2015


  • Cell cycle
  • Chaperonemediated autophagy
  • Cyclin-dependent kinases
  • Hematopoietic stem cells
  • Hypoxia-inducible factor-1
  • Minichromosome maintenance helicase
  • Neural stem cells

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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