Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-α-acetyltransferase

Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-α-acetyltransferase
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DOI:
10.1186/1471-2091-7-13
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发表时间:
2006-04-25
期刊:
影响因子:
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通讯作者:
Lillehaug, Johan R.
Lillehaug, Johan R.
中科院分区:
生物4区
文献类型:
--
作者:
Arnesen, Thomas;Betts, Matthew J.;Lillehaug, Johan R.

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背景:蛋白质乙酰化被越来越多地认为是调节多种细胞功能的重要机制。已经表征了几种人类蛋白质乙酰转移酶,它们中的大多数催化组蛋白和转录因子的ε-乙酰化。我们最近描述了人类蛋白乙酰转移酶hARD 1(人类逮捕缺陷1)。hARD 1与人N-乙酰基转移酶(N-Acetyl Transferase Human,NATH)相互作用形成复合物,表达蛋白质N-末端乙酰化活性。编码hARD 2的基因最有可能来源于真兽目哺乳动物特异性反转录转座事件。hARD 2 mRNA和蛋白质在几种人细胞系中表达。免疫沉淀实验表明,hARD 2蛋白可能与NATH相互作用,这表明hARD 2-NATH复合物可能是人类细胞中蛋白质N-α-乙酰化的原因。在NB 4细胞中,经维甲酸诱导分化后,内源性hARD 1和NATH蛋白水平下降,而hARD 2蛋白水平稳定。与只有一个ARD的低等生物相比,ARD 2可能补充ARD 1的功能,为人类细胞中的蛋白质N-α-乙酰化增加了更多的灵活性和复杂性。
Background: Protein acetylation is increasingly recognized as an important mechanism regulating a variety of cellular functions. Several human protein acetyltransferases have been characterized, most of them catalyzing epsilon-acetylation of histones and transcription factors. We recently described the human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N-terminal aacetylation activity.Results: We here describe a human protein, hARD2, with 81% sequence identity to hARD1. The gene encoding hARD2 most likely originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA and protein are expressed in several human cell lines. Immunoprecipitation experiments show that hARD2 protein potentially interacts with NATH, suggesting that hARD2-NATH complexes may be responsible for protein N-alpha-acetylation in human cells. In NB4 cells undergoing retinoic acid mediated differentiation, the level of endogenous hARD1 and NATH protein decreases while the level of hARD2 protein is stable.Conclusion: A human protein N-alpha-acetyltransferase is herein described. ARD2 potentially complements the functions of ARD1, adding more flexibility and complexity to protein N-alpha-acetylation in human cells as compared to lower organisms which only have one ARD.