HIF-1 regulation: not so easy come, easy go.
The hypoxia-inducible factor-1 (HIF-1) is the master regulator of the cellular response to hypoxia and its expression levels are tightly controlled through synthesis and degradation. It is widely accepted that HIF-1alpha protein accumulation during hypoxia results from inhibition of its oxygen-dependent degradation by the von Hippel Lindau protein (pVHL) pathway. However, recent data describe new pVHL- or oxygen-independent mechanisms for HIF-1alpha degradation. Furthermore, the hypoxia-induced increase in HIF-1alpha levels is facilitated by the continued translation of HIF-1alpha during hypoxia despite the global inhibition of protein translation. Recent work has contributed to an increased understanding of the mechanisms that control the translation and degradation of HIF-1alpha under both normoxic and hypoxic conditions.
Yee Koh
Mei
M
Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Spivak-Kroizman
Taly R
TR
Powis
Garth
G
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D025841:Small Ubiquitin-Related Modifier Proteins; C459591:USP20 protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D043222:Ubiquitin Thiolesterase