Sci. STKE, 10 December 2002
Hypoxia Hydroxylation, Ubiquitination, and Now Acetylation
Hypoxia stimulates a transcriptional program partly mediated by the stabilization of the hypoxia-inducible factor-1α (HIF-1α), which then associates with HIF-1β and acts as a transcriptional regulator stimulating genes involved in response and adaptation to reduced oxygen (see Seta et al.). Under normoxia conditions, HIF-1α is already known to be regulated by hydroxylation and ubiquitin-mediated degradation. Hydroxylation promotes the interaction between HIF-1α and the von Hippel-Lindau tumor suppressor gene product (pVHL), leading to degradation by the ubiquitin-proteasome pathway. Jeong et al. show that the oxygen-dependent degradation domain (ODD) of HIF-1α interacted with the acetylase ARD1. In transfected cells and in biochemical experiments, ARD1 acetylated HIF-1α, decreasing its activity in reporter gene assays and promoting its interaction with pVHL and its destabilization. ARD1 expression was decreased in response to hypoxia, while acetylation of HIF-1α decreased and the amount of HIF-1α protein increased. Thus, acetylation of HIF-1α may be yet another mechanism by which the transcriptional response to oxygen levels is regulated.
K. A. Seta, Z. Spicer, Y. Yuan, G. Lu, D. E. Millhorn, Responding to hypoxia: Lessons from a model cell line. Science's STKE (2002), http://stke.sciencemag.org/cgi/content/full/sigtrans;2002/146/re11. [Abstract] [Full Text]
J.-W. Jeong, M.-K. Bae, M.-Y. Ahn, S.-H. Kim, T.-K. Sohn, M.-H. Bau, M.-A. Yoo, E. J. Song, K.-J. Lee, K.-W. Kim, Regulation and destabilization of HIF-1α by ARD1-mediated acetylation. Cell 111, 709-720 (2002). [Online Journal]
Citation: Hydroxylation, Ubiquitination, and Now Acetylation. Sci. STKE 2002, tw466 (2002).
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