Acetylation of nuclear receptors in cellular growth and apoptosis
Acetylation of nuclear receptors in cellular growth and apoptosis
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DOI：
10.1016/j.bcp.2004.05.037
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发表时间：
2004-09-15
影响因子：
5.8
通讯作者：
Pestell, RG
中科院分区：
文献类型：
--
作者：
Fu, MF;Wang, CG;Pestell, RG
染色质组蛋白的翻译后修饰是转录调控的关键机制。组蛋白乙酰化与甲基化、磷酸化、泛素化、聚氧化、糖基化和ADP核糖基化一起，通过修饰核心组蛋白和非组蛋白转录因子来调节许多基因的活性。表观遗传蛋白修饰在DNA修复、蛋白稳定性、核易位、蛋白-蛋白相互作用以及细胞增殖、分化和凋亡调控等多个细胞过程中发挥重要作用。组蛋白乙酰转移酶修饰组蛋白、辅激活因子、核转运蛋白、结构蛋白、细胞周期成分和转录因子，包括p53和核受体。雌激素，pparγ和雄激素受体是核受体（NR）超家族的成员。雄激素受体（AR）和雌激素受体α (er α)在物种和其他NR之间保守的基序上直接被组蛋白乙酰化转移酶乙酰化。在AR和er α乙酰化基序内的赖氨酸残基点突变已在前列腺癌和乳腺癌组织中被发现。NR的乙酰化控制着配体敏感性和激素拮抗剂反应。AR可被p300、P/CAF和TIP60乙酰化，在培养细胞和体内，AR的乙酰化可调节共调节剂的募集和受体的生长特性。AR乙酰化模拟突变体表达与细胞周期靶基因启动子特异性改变相关的细胞凋亡减少和生长特性增强。细胞周期控制蛋白，包括细胞周期蛋白，反过来改变转录因子和核受体对靶基因启动子的通路。(C) 2004爱思唯尔公司版权所有。
Post-translational modification of chromatin histones governs a key mechanism of transcriptional regulation. Histone acetylation, together with methylation, phosphorylation, ubiquitylation, sumoylation, glycosylation, and ADP ribosylation, modulate the activity of many genes by modifying both core histones and non-histone transcription factors. Epigenetic protein modification plays an important role in multiple cellular processes including DNA repair, protein stability, nuclear translocation, protein-protein interactions, and in regulation of cellular proliferation, differentiation and apoptosis.Histone acetyltransferases modify histones, coactivators, nuclear transport proteins, structural proteins, cell cycle components and transcription factors including p53 and nuclear receptors. The estrogen, PPARgamma and androgen receptor are members of the nuclear receptor (NR) superfamily. The androgen receptor (AR) and estrogen receptor alpha (ERalpha) are directly acetylated by histone acetyltransferases at a motif that is conserved between species and other NR. Point mutations at the lysine residue within the acetylation motif of the AR and ERalpha have been identified in prostate cancer as well as in breast cancer tissue. Acetylation of the NR governs ligand sensitivity and hormone antagonist responses. The AR is acetylated by p300, P/CAF and TIP60 and acetylation of the AR regulates co-regulator recruitment and growth properties of the receptors in cultured cells and in vivo. AR acetylation mimic mutants convey reduced apoptosis and enhanced growth properties correlating with altered promoter specificity for cell-cycle target genes. Cell-cycle control proteins, including cyclins, in turn alter the access of transcription factors and nuclear receptors to the promoters of target genes. (C) 2004 Elsevier Inc. All rights reserved.