Nonhistone protein acetylation as cancer therapy targets.
Nonhistone protein acetylation as cancer therapy targets.
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DOI：
10.1586/era.10.62
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发表时间：
2010-06
影响因子：
3.3
通讯作者：
Jiang SW
中科院分区：
文献类型：
--
作者：
Singh BN;Zhang G;Hwa YL;Li J;Dowdy SC;Jiang SW
乙酰化和去乙酰化是相互抵消的，翻译后修饰会影响大量组蛋白和非组蛋白。组蛋白乙酰化对染色质结构和动力学的修饰以及基因转录调控的重要性已得到充分认识。越来越多的非组蛋白已被确定为乙酰化靶点，这些蛋白中的可逆赖氨酸乙酰化在mRNA稳定性、蛋白质定位和降解、蛋白质-蛋白质和蛋白质- dna相互作用的调节中起着重要作用。组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（hdac）在转录机制中的募集是控制细胞增殖、分化和凋亡的基因动态调控的关键因素。许多被乙酰化靶向的非组蛋白是癌基因或肿瘤抑制基因的产物，直接参与肿瘤发生、肿瘤进展和转移。HDAC的异常活性已在几种类型的癌症中得到证实，HDAC抑制剂（HDACi）已被用于治疗目的。在此，我们回顾了该领域已发表的文献，并提供了非组蛋白乙酰化的调控和功能的最新信息。在集中讨论乙酰基片段添加和去除的分子机制和途径的同时，也讨论了HDACi的治疗方式。
Acetylation and deacetylation are counteracting, post-translational modifications that affect a large number of histone and nonhistone proteins. The significance of histone acetylation in the modification of chromatin structure and dynamics, and thereby gene transcription regulation, has been well recognized. A steadily growing number of nonhistone proteins have been identified as acetylation targets and reversible lysine acetylation in these proteins plays an important role(s) in the regulation of mRNA stability, protein localization and degradation, and protein–protein and protein–DNA interactions. The recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular proliferation, differentiation and apoptosis. Many nonhistone proteins targeted by acetylation are the products of oncogenes or tumor-suppressor genes and are directly involved in tumorigenesis, tumor progression and metastasis. Aberrant activity of HDACs has been documented in several types of cancers and HDAC inhibitors (HDACi) have been employed for therapeutic purposes. Here we review the published literature in this field and provide updated information on the regulation and function of nonhistone protein acetylation. While concentrating on the molecular mechanism and pathways involved in the addition and removal of the acetyl moiety, therapeutic modalities of HDACi are also discussed.
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