Department of Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, 78957, USA.
EMBO Rep. 2011 Sep 1;12(9):924-30. doi: 10.1038/embor.2011.140.
Ubiquitin-specific protease 22 (USP22) edits the histone code by deubiquitinating H2A and H2B as part of the mammalian SAGA (Spt-Ada-Gcn5) complex, and is required for transcriptional regulation and normal cell-cycle progression. Here, we show that USP22 affects the expression of p21 by altering far upstream element (FUSE)-binding protein 1 (FBP1) ubiquitination, as ablation of USP22 leads to increased FBP1 ubiquitination and decreased FBP1 protein occupancy at the p21 gene. Surprisingly, increased polyubiquitination of FBP1 does not alter its protein stability, but instead modulates the stable recruitment of FBP1 to target loci. Our results indicate a mechanism by which USP22 regulates cell proliferation and tumorigenesis.
泛素特异性蛋白酶 22（USP22）作为哺乳动物 SAGA（Spt-Ada-Gcn5）复合物的一部分，通过去泛素化 H2A 和 H2B 来编辑组蛋白密码，并且是转录调控和正常细胞周期进程所必需的。在这里，我们表明 USP22 通过改变远上游元件（FUSE）结合蛋白 1（FBP1）的泛素化来影响 p21 的表达，因为 USP22 的缺失会导致 FBP1 泛素化增加和 p21 基因处的 FBP1 蛋白占有率降低。令人惊讶的是，FBP1 的多泛素化增加不会改变其蛋白质稳定性，而是调节 FBP1 稳定地募集到靶位。我们的结果表明了 USP22 调节细胞增殖和肿瘤发生的一种机制。
