Regulation of cell proliferation by hypoxia-inducible factors.
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.
Department of Internal Medicine, Division of Cardiology, The University of Texas Southwestern Medical Center, Dallas, Texas; and.
Maimon E
ME
Hubbi
Departments of Pediatrics, Medicine, Oncology, Radiation Oncology and Biological Chemistry; Vascular Program, Institute for Cell Engineering; and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland gsemenza@jhmi.edu.
Gregg L
GL
Semenza
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D006801:Humans
cell cycle; chaperone-mediated autophagy; cyclin-dependent kinases; hematopoietic stem cells; hypoxia-inducible factor-1; minichromosome maintenance helicase; neural stem cells