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Review
, 309 (12), C775-82

Regulation of Cell Proliferation by Hypoxia-Inducible Factors

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Review

Regulation of Cell Proliferation by Hypoxia-Inducible Factors

Maimon E Hubbi et al. Am J Physiol Cell Physiol.

Abstract

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.

Keywords: cell cycle; chaperone-mediated autophagy; cyclin-dependent kinases; hematopoietic stem cells; hypoxia-inducible factor-1; minichromosome maintenance helicase; neural stem cells.

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