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Cell Signal. 2005 Jan;17(1):1-9.

Signalling via the hypoxia-inducible factor-1alpha requires multiple posttranslational modifications.

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Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France.


Cellular hypoxia, a local decrease in the oxygen concentration below normal (21%) atmospheric concentrations, occurs in both physiological and pathological situations. The transcriptional complex Hypoxia-Inducible Factor-1 (HIF-1) is the key player in the signalling pathway that controls the hypoxic response of mammalian cells. Tight regulation of this response involves posttranslational modification of the alpha subunit of HIF-1. Hydroxylation, ubiquitination, acetylation, S-nitrosation and phosphorylation have been shown to determine its half-life and/or transcriptional activity. The precise spatio-temporal occurrence of these multiple modifications is still not fully understood but is dependent on the microenvironment and determines the driving force of variable cellular responses.

[Indexed for MEDLINE]

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