Open AccessRegulatory mechanisms of hypoxia‐inducible factor 1 activity: Two decades of knowledge
Author(s) -
Koyasu Sho,
Kobayashi Minoru,
Goto Yoko,
Hiraoka Masahiro,
Harada Hiroshi
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13483
Subject(s) - hypoxia inducible factors , proteolysis , hypoxia (environmental) , biology , gene , ubiquitin , activator (genetics) , protein subunit , microbiology and biotechnology , cancer research , genetics , chemistry , oxygen , biochemistry , enzyme , organic chemistry
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.