SUMO-1 modification activates the transcriptional response of p53
SUMO-1 modification activates the transcriptional response of p53
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DOI：
10.1093/emboj/18.22.6455
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发表时间：
1999-11-15
期刊：
影响因子：
11.4
通讯作者：
Hay, RT
中科院分区：
文献类型：
--
作者：
Rodriguez, MS;Desterro, JMP;Hay, RT
p53肿瘤抑制蛋白受泛素介导的蛋白酶体降解的调节。在正常细胞中，p53被Mdm 2泛素连接酶组成型泛素化，当p53应答被应激信号激活时，由于该降解途径的抑制，p53水平升高。在这里，我们表明，p53被修饰的小泛素样蛋白SUMO-1在一个单一的网站，K386，在蛋白质的C-末端。体外修饰仅需要SUMO-1，SUMO-1活化酶和ubc 9，SUMO-1和泛素修饰不竞争p53中相同的赖氨酸受体位点。SUMO-1的过表达激活野生型p53的转录活性，但不激活SUMO-1受体位点已突变的K386 R p53。因此，SUMO-1修饰途径作为p53反应的潜在调节剂，并可能代表用于开发治疗上有用的p53反应调节剂的新靶点。
The p53 tumour suppressor protein is regulated by ubiquitin-mediated proteasomal degradation. In normal cells p53 is constitutively ubiquitylated by the Mdm2 ubiquitin ligase, When the p53 response is activated by stress signals p53 levels rise due to inhibition of this degradative pathway. Here we show that p53 is modified by the small ubiquitin-like protein SUMO-1 at a single site, K386, in the C-terminus of the protein. Modification in vitro requires only SUMO-1, the SUMO-1 activating enzyme and ubc9, SUMO-1 and ubiquitin modification do not compete for the same lysine acceptor sites in p53, Overexpression of SUMO-1 activates the transcriptional activity of wildtype p53, but not K386R p53 where the SUMO-1 acceptor site has been mutated. The SUMO-1 modification pathway therefore acts as a potential regulator of the p53 response and may represent a novel target for the development of therapeutically useful modulators of the p53 response.