Histone acetyltransferases and histone deacetylases in B- and T-cell development, physiology and malignancy.
Histone acetyltransferases and histone deacetylases in B- and T-cell development, physiology and malignancy.
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B-和T细胞发育，生理和恶性肿瘤中的组蛋白乙酰转移酶和组蛋白脱乙酰基酶。
DOI：
10.18632/genesandcancer.65
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Gilmore TD
中科院分区：
文献类型：
--
作者：
Haery L;Thompson RC;Gilmore TD
从造血前体发育B和T细胞以及调节这些免疫细胞的功能是复杂的过程，其涉及高度调节的信号传导途径和转录控制。引起这些发育过程的信号传导途径和基因表达模式部分地由两类相反的广泛酶调节剂协调：组蛋白乙酰转移酶（HAT）和组蛋白脱乙酰酶（HDAC）。HAT和HDAC可以通过改变组蛋白乙酰化以修饰染色质结构以及通过调节非组蛋白底物（包括一系列免疫细胞转录因子）的活性来调节基因转录。除了它们在正常B和T细胞中的作用之外，HAT和HDAC活性的失调与多种B-和T-细胞恶性肿瘤相关。在这篇综述中，我们描述了HAT和HDAC在正常B-和T-细胞生理学中的作用，描述了与淋巴瘤和白血病有关的HAT和HDAC的突变和失调，并讨论了HAT和HDAC抑制剂已被探索为白血病和淋巴瘤的治疗选择。
The development of B and T cells from hematopoietic precursors and the regulation of the functions of these immune cells are complex processes that involve highly regulated signaling pathways and transcriptional control. The signaling pathways and gene expression patterns that give rise to these developmental processes are coordinated, in part, by two opposing classes of broad-based enzymatic regulators: histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs can modulate gene transcription by altering histone acetylation to modify chromatin structure, and by regulating the activity of non-histone substrates, including an array of immune-cell transcription factors. In addition to their role in normal B and T cells, dysregulation of HAT and HDAC activity is associated with a variety of B- and T-cell malignancies. In this review, we describe the roles of HATs and HDACs in normal B- and T-cell physiology, describe mutations and dysregulation of HATs and HDACs that are implicated lymphoma and leukemia, and discuss HAT and HDAC inhibitors that have been explored as treatment options for leukemias and lymphomas.