Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 19 January 2010
Vol. 3, Issue 105, p. ec23
[DOI: 10.1126/scisignal.3105ec23]

EDITORS' CHOICE

Cell Biology Not Just Activated by Hypoxia

Wei Wong

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).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882