Arnesen Thomas, Kong Xianguo, Evjenth Rune, Gromyko Darina, Varhaug Jan Erik, Lin Zhao, Sang Nianli, Caro Jaime, Lillehaug Johan R
Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
FEBS Lett. 2005 Nov 21;579(28):6428-32. doi: 10.1016/j.febslet.2005.10.036. Epub 2005 Nov 2.
Hypoxia inducible factor-1 alpha (HIF-1 alpha) is a central component of the cellular responses to hypoxia. Hypoxic conditions result in stabilization of HIF-1 alpha and formation of the transcriptionally active HIF-1 complex. It was suggested that mammalian ARD1 acetylates HIF-1 alpha and thereby enhances HIF-1 alpha ubiquitination and degradation. Furthermore, ARD1 was proposed to be down-regulated in hypoxia thus facilitating the stabilization of HIF-1 alpha. Here we demonstrate that the level of human ARD1 (hARD1) protein is not decreased in hypoxia. Moreover, hARD1 does not acetylate and destabilize HIF-1 alpha. However, we find that hARD1 specifically binds HIF-1 alpha, suggesting a putative, still unclear, connection between these proteins.
缺氧诱导因子-1α(HIF-1α)是细胞对缺氧反应的核心成分。缺氧条件导致HIF-1α稳定并形成具有转录活性的HIF-1复合物。有人提出哺乳动物ARD1使HIF-1α乙酰化,从而增强HIF-1α的泛素化和降解。此外,有人认为ARD1在缺氧时下调,从而促进HIF-1α的稳定。在此我们证明,缺氧时人ARD1(hARD1)蛋白水平并未降低。此外,hARD1不会使HIF-1α乙酰化并使其不稳定。然而,我们发现hARD1特异性结合HIF-1α,表明这些蛋白之间存在一种尚不清楚的假定联系。