Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes
Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes
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DOI：
10.1073/pnas.172511699
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发表时间：
2002-10-15
影响因子：
11.1
通讯作者：
Eisenman, RN
中科院分区：
文献类型：
--
作者：
Hook, SS;Orian, A;Eisenman, RN
组蛋白去乙酰化酶（HDAC）被认为是转录抑制的关键介质。然而，II类HDAC的生理靶点和翻译后修饰在很大程度上是未知的。在这里，我们表明，HDAC 6的C末端是必要的和足够的特异性协会与聚泛素。该区域含有一个推定的锌指，但缺乏显着的相似性，其他已知的泛素结合结构域。因此，我们将该区域指定为PAZ结构域，即多聚泛素相关锌指。尽管PAZ结构域与去泛素化酶的锌指具有同源性，但我们发现在免疫纯化后与HDAC 6相关的去泛素化活性是不确定的。我们还表明，HDAC 5和HDAC 6在体外和体内都是泛素化的。然而，这两种蛋白质在体内是稳定的，并且似乎不被蛋白酶体快速降解。因此，HDAC 6通过泛素缀合、多聚泛素结合和与去泛素化酶的共纯化与泛素系统连接。
Histone deacetylases (HDACs) are thought to function as critical mediators of transcriptional repression. However, the physiological-targets and posttranslational modifications of the class II HDACs are largely unknown. Here we show that the C terminus of HDAC 6 is both necessary and sufficient for specific association with polyubiquitin. This region contains a putative zinc finger but lacks significant similarity to other known ubiquitin binding domains. Thus, we have designated this region as a PAZ domain, for Polyubiquitin Associated Zinc finger. Although the PAZ domain possesses homology with the zinc finger of deubiquitinating enzymes, it is dispensable for the deubiquitinating activity we find associated with HDAC6 following immunopurification. We also show that both HDAC 5 and HDAC 6 are ubiquitinated in vitro and in vivo. However, both of these proteins are stable in vivo and do not appear to be targeted for rapid degradation by the proteasome. Thus, HDAC6 is linked to the ubiquitin system via ubiquitin conjugation, polyubiquitin binding, and copurification with deubiquitinating enzymes.