Transduction pathways involved in hypoxia-inducible FACTOR-1 phosphorylation and activation

Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activ ated by hypoxia and involved in the adaptative response of the cell to oxyg en deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes coding for glycolytic enzymes and angiogenic factors. To be active H IF-1 must be phosphorylated. HIF-1 is a substrate for various kinase pathwa ys including PI-3K and the MAP kinases ERK and p38. Several transduction pa thways have been proposed which act downstream of putative oxygen sensors a nd lead to the activation of these kinases. In this review, we summarize so me of the latest advances describing the possible signaling pathways leadin g to HIF-1 phosphorylation and subsequent activation. The physiological rel evance of these regulations is also discussed. (C) 2001 Elsevier Science In c.