在研究中，研究人员证实SUMO化激活酶UBA2在肝癌细胞和临床样本中高水平表达。沉默UBA2表达可在一定程度上抑制细胞增殖。为了阐明UBA2的功能，他们利用了一种大规模蛋白质组学策略来鉴别HepG2中的SUMO化靶蛋白，确定了对照样本中没有的827种潜在SUMO1修饰蛋白的特征。研究人员在基因表达过程中富集了这些蛋白。通过免疫沉淀——Western Blotting确证了12个候选蛋白是SUMO1修饰蛋白。进一步鉴别了SUMO化TFII-I蛋白的特征，确定SUMO1是在K221和K240位点让TFII-I发生了SUMO化修饰。PIAS4是负责TFII-I SUMO化的一个E3连接酶，SENP2则在HepG2细胞中负责TFII-I 去SUMO化。SUMO化可抑制TFII-I与阻遏蛋白HDAC3结合，由此提高TFII-I的转录活性。研究人员进一步证实了SUMO化对于TFII-I促进细胞增殖和克隆形成起至关重要的作用。研究结果有助于了解SUMO化在肝癌形成中的作用。

原文链接：

functional Proteomics Study Reveals SUMOylation of TFII-I is Involved in Liver Cancer Cell Proliferation

原文摘要：

SUMOylation has emerged as a new regulatory mechanism for proteins involved in multiple physiological ａnd pathological processes. However, the detailed function of SUMOylation in liver cancer is still elusive. This study reveals that the SUMOylation-activating enzyme UBA2 is highly expressed in liver cancer cells ａnd clinical samples. Silencing of UBA2 expression could to some extent suppress cell proliferation. To elucidate the function of UBA2, we used a large scale proteomics strategy to identify SUMOylation targets in HepG2 cells. We characterized 827 potential SUMO1-modified proteins that were not present in the control samples. These proteins were enriched in gene expression processes. Twelve candidates were validated as SUMO1-modified proteins by immunoprecipitation-Western blotting. We further characterized SUMOylated protein TFII-I that was identified in this study ａnd determined that TFII-I was modified by SUMO1 at K221 ａnd K240. PIAS4 was an E3 ligase for TFII-I SUMOylation, ａnd SENP2 was responsible for deSUMOylating TFII-I in HepG2 cells. SUMOylation reduced TFII-I binding to its repressor HDAC3 ａnd thus promoted its transcriptional activity. We further show that SUMOylation is critical for TFII-I to promote cell proliferation ａnd colony formation. Our findings contribute to understanding the role of SUMOylation in liver cancer development

DOI: 10.1021/acs.jproteome.5b00062

作者：贺福初教授