UAF1 Is a Subunit of Multiple Deubiquitinating Enzyme Complexes
UAF1 Is a Subunit of Multiple Deubiquitinating Enzyme Complexes
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DOI：
10.1074/jbc.m808430200
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发表时间：
2009-02-20
影响因子：
4.8
通讯作者：
D'Andrea, Alan D.
中科院分区：
文献类型：
--
作者：
Cohn, Martin A.;Kee, Younghoon;D'Andrea, Alan D.
泛素化和去泛素化之间的平衡调节许多细胞过程和途径，并且特定的去泛素化酶通常在控制这种平衡中起决定性作用。我们最近报道了USP 1去泛素化酶，其通过去泛素化途径的中心参与者FANCD 2来调节Fanconi贫血途径，通过形成稳定的USP 1/UAF 1蛋白复合物被含有WD 40重复的UAF 1蛋白激活。在这里，我们提出了两个新的多亚基去泛素化酶复合物的分离，分别含有USP 12和USP 46。两种复合物都含有UAF 1蛋白作为真正的亚基。有趣的是，UAF 1调节两种酶复合物的酶活性，这表明这种激活蛋白可能调节人类去泛素化酶的一个亚类。我们推测，其他WD 40蛋白也可能与其他人类去泛素化酶形成复合物，从而调节其活性和底物特异性。
A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific deubiquitinating enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 deubiquitinating enzyme, which regulates the Fanconi anemia pathway by deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both enzyme complexes, suggesting that this activator protein may regulate a subclass of human deubiquitinating enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human deubiquitinating enzymes and thereby regulate their activity and substrate specificity.