Signalling via the hypoxia-inducible factor-1α requires multiple posttranslational mofications

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. (C) 2004 Elsevier Inc. All rights reserved.