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Abstract：
Post-translational modifications of the histone H2A represent an important mechanism by which cells modulate the structure and function of chromatin. Ubiquitination at K119 of histone H2A is associated transcriptional repression, which is shown to be regulated by deubiquitinases (DUBs). Here, we performed a screen to identify novel DUBs for histone H2A. Although RNAi-mediated knockdown of USP28, USP32 and USP36 showed that their depletion resulted in the increase of ub-K119-H2A, only USP28-depleted cells showed increased cell proliferation. Notably, USP28 knockdown cells had decreased expression of p53, p21 and p16INK4a, suggesting that the effect of USP28 on cell proliferation was mediated by regulating the expression of p53, p21 and p16INK4a. In summary, we have shown that USP28 is a deubiquitinase for histone H2A and is involved in regulation of cell proliferation. Thus, USP28 represents a potentially novel therapeutic target for cancer.
摘要：
组蛋白H2A的翻译后修饰代表了细胞调节染色质结构和功能的重要机制。组蛋白H2A的K119泛素化与转录抑制有关，它被证明是由去泛素酶（DUB）调节。这里,我们进行了筛选以鉴定组蛋白H2A的新DUB。尽管RNAi介导的USP28，USP32和USP36的敲除表明它们的消耗导致了ub-K119-H2A的增加，只有USP28耗尽的细胞显示细胞增殖增加.值得注意的是,USP28敲低细胞中p53、p21和p16INK4a的表达降低,表明USP28对细胞增殖的影响是通过调节p53，p21和p16INK4a的表达来介导的。总之,我们已经证明USP28是组蛋白H2A的去泛素酶,并且参与细胞增殖的调节。因此，USP28代表癌症的潜在新型治疗靶标。
