Lysine deacetylase (KDAC) regulatory pathways: an alternative approach to selective modulation.
Lysine deacetylase (KDAC) regulatory pathways: an alternative approach to selective modulation.
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DOI：
10.1002/cmdc.201300444
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发表时间：
2014-03
期刊：
影响因子：
3.4
通讯作者：
Van Dyke, Michael W.
中科院分区：
文献类型：
--
作者：
Van Dyke, Michael W.
关键词：
蛋白赖氨酸脱乙酰酶（KDAC），包括经典的Zn 2+依赖性组蛋白脱乙酰酶（HDAC）和需要烟酰胺腺嘌呤二核苷酸（NAD+）的沉默调节蛋白，是在许多生物过程中发挥关键作用的酶，特别是响应于内部和外部线索的全局基因表达程序的表观遗传调节。KDAC的失调是几种人类疾病的特征，包括慢性代谢、神经退行性和心血管疾病以及许多癌症。这导致了KDAC调节剂的开发，其中两种（HDAC抑制剂伏立诺他和罗米地辛）已被批准用于治疗皮肤T细胞淋巴瘤。就其性质而言，现有的KDAC调节剂是相对非特异性的，导致泛KDAC变化和不期望的副作用。鉴于KDAC在许多水平上受到调控，包括转录、翻译后、亚细胞定位以及通过与其他蛋白质的复合，因此应该可以通过操纵内源性信号传导途径来影响特定的KDAC活性。在这篇小综述中，我们讨论了我们目前对KDAC活性的细胞控制的了解及其药理学调节的实例。
Protein lysine deacetylases (KDACs), including the classic Zn2+-dependent histone deacetylases (HDACs) and the nicotinamide adenine dinucleotide (NAD+)-requiring sirtuins, are enzymes that play critical roles in numerous biological processes, particularly the epigenetic regulation of global gene expression programs in response to internal and external cues. Dysregulation of KDACs is characteristic of several human diseases, including chronic metabolic, neurodegenerative, and cardiovascular diseases and many cancers. This has led to the development of KDAC modulators, two of which (HDAC inhibitors vorinostat and romidepsin) have been approved for the treatment of cutaneous Tcell lymphoma. By their nature, existing KDAC modulators are relatively nonspecific, leading to pan-KDAC changes and undesired side effects. Given that KDACs are regulated at many levels, including transcriptional, posttranslational, subcellular localization, and through their complexation with other proteins, it should be possible to affect specific KDAC activity through manipulation of endogenous signaling pathways. In this Minireview, we discuss our present knowledge of the cellular controls of KDAC activity and examples of their pharmacologic regulation.
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影响因子：
56.9
作者：
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通讯作者：
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DOI：
10.1111/j.1349-7006.2001.tb02153.x
发表时间：
2001-12
期刊：
Japanese journal of cancer research : Gann
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作者：
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Accili D