Acetyltransferase machinery conserved in p300/CBP-family proteins

Acetyltransferase machinery conserved in p300/CBP-family proteins
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DOI:
10.1038/sj.onc.1205283
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发表时间:
2002-03
期刊:
影响因子:
8
通讯作者:
L Wuchao Yuan;A. Giordano
L Wuchao Yuan;A. Giordano
中科院分区:
医学1区
文献类型:
--
作者:
L Wuchao Yuan;A. Giordano

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CREB结合蛋白(CBP)和p300是高度保守的功能相关的转录共激活因子和组蛋白/蛋白乙酰转移酶。它们是肿瘤抑制因子,参与多种生理活动,在不同的信号转导途径中发挥整合作用。在这项研究中,在现有的蛋白质数据库中,已经鉴定了11个与p300的氨基酸序列高度同源的不同蛋白质。所有这11种蛋白质都属于动物或植物多细胞生物体(高等真核生物)。通过序列比对和模式搜索进一步验证了p300/CBP结构域在这些蛋白中的保守性。HAT功能所需的p300/CBP结构域,包括PHD、可能的CoA结合结构域和ZZ结构域,在这11种蛋白质中都是保守的。这与以往的功能分析结果一致,表明它们是一个乙酰基转移酶家族,即p300/CBP乙酰基转移酶(PCAT)。PCAT蛋白的Taz结构域(TAZ1和/或TAZ2)可能允许它们通过直接招募转录因子、随后乙酰化它们或指导核小体组蛋白的靶向乙酰化来参与转录调控。
CREB-binding protein (CBP) and p300 are highly conserved and functionally related transcription coactivators and histone/protein acetyltransferases. They are tumor suppressors, participate in a wide variety of physiological events, and serve as integrators among different signal transduction pathways. In this study, 11 distinct proteins that have a high degree of homology with the amino acid sequence of p300 have been identified in current protein databases. All of these 11 proteins belong to either animal or plant multicellular organisms (higher eucaryotes). Conservation of p300/CBP domains among these proteins was examined further by sequence alignment and pattern search. The domains of p300/CBP that are required for the HAT function, including PHD, putative CoA-binding, and ZZ domains, are conserved in all of these 11 proteins. This observation is consistent with the previous functional assays and indicates that they are a family of acetyltransferases, ie p300/CBP acetyltransferases (PCAT). TAZ domains (TAZ1 and/or TAZ2) of PCAT proteins may allow them to participate in transcription regulation by either directly recruiting transcription factors, acetylating them subsequently, or directing targeted acetylation of nucleosomal histones.