Regulatory mechanisms of hypoxia‐inducible factor 1 activity: Two decades of knowledge

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  • 子安, 翔
    Laboratory of Cancer Cell Biology, Department of Genome Dynamics, Radiation Biology Center, Kyoto University・Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • 小林, 稔
    Laboratory of Cancer Cell Biology, Department of Genome Dynamics, Radiation Biology Center, Kyoto University
  • 後藤, 容子
    Department of Radiation Oncology and Image‐applied Therapy, Kyoto University Graduate School of Medicine
  • 平岡, 眞寛
    Department of Radiation Oncology and Image‐applied Therapy, Kyoto University Graduate School of Medicine
  • 原田, 浩
    Laboratory of Cancer Cell Biology, Department of Genome Dynamics, Radiation Biology Center, Kyoto Universit・Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency (JST)

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  • Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge

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Hypoxia‐inducible factor 1 (HIF‐1) is a transcriptional activator of various genes related to cellular adaptive responses to hypoxia. Dysfunctions in the regulatory systems of HIF‐1 activity have been implicated in the pathogenesis of various diseases including malignant tumors and, thus, elucidating the molecular mechanisms underlying the activation of HIF‐1 is eagerly desired for the development of novel anti‐cancer strategies. The importance of oxygen‐dependent and ubiquitin‐mediated proteolysis of the regulatory subunit of HIF‐1 (HIF‐1α) was first reported in 1997. Since then, accumulating evidence has shown that HIF‐1α may become stable and active even under normoxic conditions; for example, when disease‐associated genetic and functional alterations in some genes trigger the aberrant activation of HIF‐1 regardless of oxygen conditions. We herein review the last two decades of knowledge, since 1997, on the regulatory mechanisms of HIF‐1 activity from conventional oxygen‐ and proteolysis‐dependent mechanisms to up‐to‐the‐minute information on cancer‐associated genetic and functional alteration‐mediated mechanisms.

収録刊行物

  • Cancer Science

    Cancer Science 109 (3), 560-571, 2018-03-03

    Blackwell Publishing Ltd

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