Sci. Signal., 19 January 2010
Cell Biology Not Just Activated by Hypoxia
Science Signaling, AAAS, Washington, DC 20005, USA
Hypoxia inducible factor 1 (HIF-1) is an evolutionarily conserved transcription factor that mediates cellular responses to low oxygen availability. In Caenorhabditis elegans, oxygen-dependent hydroxylation of proline residues in HIF-1 by Egg Laying 9 (EGL-9) leads to the ubiquitination of HIF-1 by a complex containing the ubiquitin ligase von Hippel–Lindau factor 1 (VHL-1) and ultimately the proteasomal degradation of HIF-1. Hypoxic conditions block prolyl hydroxylation of HIF-1, thereby causing HIF-1 to accumulate, translocate to the nucleus, and mediate gene transcription. Noting that low-oxygen environments often contain high concentrations of hydrogen sulfide (H2S), Budde and Roth investigated the effect of H2S on HIF-1 activity in C. elegans. They found that animals with a null mutation in hif-1 were more sensitive to lethal effects of H2S than were wild-type animals, whereas animals with null mutations in egl-9 or vhl-1, both of which would be expected to increase the abundance of HIF-1, were less sensitive than wild-type animals. Exposure to H2S increased the abundance of HIF-1, triggered nuclear localization of HIF-1, and increased the transcription of two HIF-1 target genes. Strikingly, the activity of a reporter gene for HIF-1 increased only in the gut after hypoxia, whereas it increased throughout the body after exposure to H2S. H2S-mediated activation of HIF-1 required EGL-9, but not VHL-1. Thus, HIF-1 is activated by H2S, which the authors point out can be produced endogenously by cells.
M. W. Budde, M. B. Roth, Hydrogen sulfide increases hypoxia-inducible factor-1 activity independently of von Hippel–Lindau tumor suppressor-1 in C. elegans. Mol. Biol. Cell 21, 212–217 (2010). [Abstract] [Full Text]
Citation: W. Wong, Not Just Activated by Hypoxia. Sci. Signal. 3, ec23 (2010).
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