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组蛋白去乙酰化酶 6 在健康和疾病中的作用。

Histone deacetylase 6 in health and disease.

机构信息

Laboratory of Molecular & Cellular Biology of Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg.

出版信息

Epigenomics. 2015;7(1):103-18. doi: 10.2217/epi.14.69.

Abstract

Histone deacetylase (HDAC)6 is a member of the class IIb HDAC family. This enzyme is zinc-dependent and mainly localized in the cytoplasm. HDAC6 is a unique isoenzyme with two functional catalytic domains and specific physiological roles. Indeed, HDAC6 deacetylates various substrates including α-tubulin and HSP90α, and is involved in protein trafficking and degradation, cell shape and migration. Consequently, deregulation of HDAC6 activity was associated to a variety of diseases including cancer, neurodegenerative diseases and pathological autoimmune response. Therefore, HDAC6 represents an interesting potential therapeutic target. In this review, we discuss structural features of this histone deacetylase, regulation of its expression and activity, biological functions, implication in human disease initiation and progression. Finally will describe novel and selective HDAC6 inhibitors.

摘要

组蛋白去乙酰化酶(HDAC)6 是 IIb 类 HDAC 家族的成员。这种酶依赖锌,并主要定位于细胞质中。HDAC6 是一种具有两个功能催化结构域的独特同工酶,具有特定的生理作用。事实上,HDAC6 去乙酰化包括α-微管蛋白和 HSP90α 在内的各种底物,并参与蛋白质运输和降解、细胞形状和迁移。因此,HDAC6 活性的失调与包括癌症、神经退行性疾病和病理性自身免疫反应在内的多种疾病有关。因此,HDAC6 是一个很有前途的治疗靶点。在这篇综述中,我们讨论了这种组蛋白去乙酰化酶的结构特征、其表达和活性的调节、生物学功能、在人类疾病发生和发展中的作用。最后将描述新型和选择性的 HDAC6 抑制剂。

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