Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1α fragments in vitro
Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1α fragments in vitro
复制标题
DOI：
10.1016/j.febslet.2006.02.012
复制
发表时间：
2006-04-03
期刊：
影响因子：
3.5
通讯作者：
Schofield, CJ
中科院分区：
文献类型：
--
作者：
Murray-Rust, TA;Oldham, NJ;Schofield, CJ
在人类中，许多对低氧的反应，包括血管生成和红细胞生成，都是由α/β异二聚体转录因子低氧诱导因子(HIF)介导的。人HIF-1α的稳定性和/或活性受到翻译后修饰的调节，包括脯氨酸和天冬酰胺羟化、磷酸化，以及据报道通过乙酰基转移酶ARD1(停滞缺陷蛋白1同源)对Lys(532)侧链的乙酰化。使用纯化的重组人ARD1(HARD1)，我们没有观察到ARD1介导的利用HIF-1α片段的Lys532的N-乙酰化。然而，从大肠杆菌中获得的重组hARD1是通过部分N-末端乙酰化产生的，并且观察到缓慢的自身介导的N-末端乙酰化。这些观察结果与其他数据表明，至少单独的hARD1不能乙酰化HIF-1α，以及最近报道的由hARD1和N-乙酰转移酶蛋白组成的异二聚体复合体的N-末端乙酰基转移酶活性的报道是一致的。(C)2006年欧洲生化学会联合会。爱思唯尔出版，版权所有。
In humans, many responses to hypoxia including angiogenesis and erythropoiesis are mediated by the alpha/beta-heterodimeric transcription factor hypoxia inducible factor (HIF). The stability and/or activity of human HIF-1 alpha are modulated by post-translational modifications including prolyl and asparaginyl hydroxylation, phosphorylation, and reportedly by acetylation of the side-chain of Lys(532) by ARD1 (arrest defective protein 1 homologue), an acetyltransferase. Using purified recombinant human ARD1 (hARD1) we did not observe ARD1-mediated N-acetylation of Lys532 using fragments of HIF-1 alpha. However, recombinant hARD1 from Escherichia coli was produced with partial N-terminal acetylation and was observed to undergo slow self-mediated N-terminal acetylation. The observations are consistent with the other data indicating that hARD1, at least alone, does not acetylate HIF-1 alpha, and with reports on the N-terminal acetyltransferase activity of a recently reported heterodimeric complex comprising hARD1 and N-acetyltransferase protein. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.