Involvement of PIAS1 in the sumoylation of tumor suppressor p53
Involvement of PIAS1 in the sumoylation of tumor suppressor p53
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DOI：
10.1016/s1097-2765(01)00349-5
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发表时间：
2001-09-01
期刊：
影响因子：
16
通讯作者：
Yasuda, H
中科院分区：
文献类型：
--
作者：
Kahyo, T;Nishida, T;Yasuda, H
研究表明，泛素样蛋白SUMO-1/ sentrin/PIC1对p53的Sumoylation作用可刺激其转录激活活性。SUMO E3连接酶是识别待水解底物的关键酶，目前尚未确定。我们通过酵母双杂交筛选分离出SUMO-1结合蛋白PIAS1（活化STAT1蛋白抑制剂）。此外，PIAS1结合p53和Ubc9， E2用于SUMO。PIAS1在环指状结构域结合p53和SUMO-1发生突变，但Ubc9没有发生突变。PIAS1在U2OS细胞和体外以结构域依赖的方式催化p53的sumo化。这些数据表明，PIAS1作为SUMO连接酶，或可能作为SUMO紧密结合的调节因子，对p53起作用。
Sumoylation of p53 by the ubiquitin-like protein, SUMO-1/ sentrin/PIC1, has been shown to stimulate its transcriptional activation activity. The SUMO E3 ligase, a key enzyme in the recognition of substrates to be sumoylated, has not yet been identified. We isolated PIAS1 (protein inhibitor of activated STAT1) as a SUMO-1 binding protein by yeast two-hybrid screening. In addition, PIAS1 bound p53 and Ubc9, the E2 for SUMO. PIAS1 that was mutated in the RING finger-like domain bound p53 and SUMO-1, but not Ubc9. PIAS1 catalyzed the sumoylation of p53 both in U2OS cells and in vitro in a domain-dependent manner. These data suggest that PIAS1 functions as a SUMO ligase, or possibly as a tightly bound regulator of it, toward p53.