The deubiquitylation activity of Ubp8 is dependent upon Scf11 and its association with the SAGA complex
The deubiquitylation activity of Ubp8 is dependent upon Scf11 and its association with the SAGA complex
复制标题
DOI：
10.1128/mcb.25.3.1173-1182.2005
复制
发表时间：
2005-02-01
影响因子：
5.3
通讯作者：
Workman, JL
中科院分区：
文献类型：
--
作者：
Lee, KK;Florens, L;Workman, JL
组蛋白尾部的共价修饰和这些修饰之间的串扰是基因调控的标志性特征。佐贺组蛋白乙酰转移酶复合物是参与这些共价修饰的最充分表征的复合物之一。最近的发现，从H2B的泛素基团的去除是由佐贺的一个组成部分，Ubp8，是有趣的，因为它分配两个翻译后修饰过程的一个复杂的。在这项工作中，我们的特点协会的Ubp8与佐贺和乙酰化和去泛素化的影响，在体外和体内对彼此。我们发现Ubp8不仅是佐贺复合物的一部分，而且它的去泛素化活性需要Ubp8与佐贺结合。此外，我们发现Ubp8与佐贺的关联需要SGF11，并且这种要求是相互的。我们还发现佐贺的乙酰化和去泛素化活性是相互独立的。然而，我们发现，预乙酰化组蛋白H2B抑制随后的去泛素化。另外。我们发现增加H2B的超液化状态抑制ARG1基因的表达。其抑制以前显示需要RAD 6泛素连接酶。总之，这些数据表明，包括ARG1在内的一些基因的表达受到细胞中组蛋白H2B泛素化平衡的调节。
Covalent modifications of the histone tails and the cross talk between these modifications are hallmark features of gene regulation. The SAGA histone acetyltransferase complex is one of the most well-characterized complexes involved in these covalent modifications. The recent finding that the removal of the ubiquitin group from H2B is performed by a component of SAGA, Ubp8, is intriguing as it assigns two posttranslation modification processes to one complex. In this work, we characterize the association of Ubp8 with SAGA and the effect that acetylation and deubiquitylation have on one another in vitro and in vivo. We found not only that Ubp8 is a part of the SAGA complex, but also that its deubiquitylation activity requires Ubp8's association with SAGA. Furthermore, we found that the Ubp8 association with SAGA requires SGFl1 and that this requirement is reciprocal. We also found that the acetylation and deubiquiqlation activities of SAGA are independent of one another. However, we found that preacetylating histone H2B inhibited subsequent deubiquitylation. Additionally. we found that increasing the ulliquitylation state of H2B inhibited the expression of the ARG1 gene. whose repression was previously shown to require the RAD6 ubiquitin ligase. Taken together, these data indicate that the expression of some genes, including ARG1, is regulated by a balance of histone H2B ubiquitylation in the cell.