HDAC6型
好斗的
组蛋白脱乙酰基酶
细胞生物学
神经退行性变
化学
泛素
陶氏病
生物
组蛋白
生物化学
医学
基因
病理
疾病
作者
Yuan-Zai Zhu,Mengkai Feng,Bo Wang,Yi-Chao Zheng,Dandan Jiang,Lijuan Zhao,M. A. A. Mamun,Huifang Kang,Hai-Qian Nie,Xiya Zhang,Ningjie Guo,Shangshang Qin,Ning Wang,Hong‐Min Liu,Ya Gao
标识
DOI:10.1016/j.biopha.2023.114438
摘要
Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins. As a result, aggresomes are formed and protein degradation is facilitated by the autophagy-lysosome pathway. This HDAC6-dependent microtubule transport can be used by cells to assemble and activate inflammasomes, which play a critical role in immune regulation. Even viruses can benefit from the carrier of HDAC6 to assist in uncoating their surfaces during their infection cycle. However, HDAC6 is also capable of blocking virus invasion and replication in a non-enzymatic manner. Given these non-enzymatic functions, HDAC6 is closely associated with various diseases, including neurodegeneration, inflammasome-associated diseases, cancer, and viral infections. Small molecule inhibitors targeting the ubiquitin binding pocket of HDAC6 have been investigated. In this review, we focus on mechanisms in non-enzymatic functions of HDAC6 and discuss the rationality and prospects of therapeutic strategies by intervening the activation of HDAC6 ZnF-UBP in concrete diseases.
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