O2 Sensing Model Further Modified

Science's STKE  05 Feb 2002:
Vol. 2002, Issue 118, pp. tw56-TW56
DOI: 10.1126/stke.2002.118.tw56

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]