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Sci. STKE, 5 February 2002
Vol. 2002, Issue 118, p. tw56
[DOI: 10.1126/stke.2002.118.tw56]


Hypoxia O2 Sensing Model Further Modified

When oxygen becomes limiting (hypoxia), mammalian cells respond by increasing transcription of genes that enhance oxygen delivery or that facilitate metabolic adjustment to reduced oxygen availability. The hypoxia-inducible transcription factor HIF-α plays a pivotal role in this adaptive response, and recent work has revealed that HIF-α activity is controlled in part by oxygen-dependent proline hydroxylation, which reduces protein stability. Lando et al. (see the Perspective by Bruick and McKnight) identify asparagine hydroxylation as a second oxygen-dependent protein modification regulating HIF-α activity and show that the critical asparagine target resides in the transactivation domain of HIF-α. Hydroxylation of this asparagine, which occurs under normal oxygen conditions, appears to suppress the transcriptional activity of HIF-α by preventing its interaction with the coactivator protein p300.

D. Lando, D. J. Peet, D. A. Whelan, J. J. Gorman, M. L. Whitelaw, Asparagine hydroxylation of the HIF transactivation domain: A hypoxic switch. Science 295, 858-861 (2002). [Abstract] [Full Text]

R. K. Bruick, S. L. McKnight, Oxygen sensing gets a second wind. Science 295, 807-808 (2002) [Full Text]

Citation: O2 Sensing Model Further Modified. Sci. STKE 2002, tw56 (2002).

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