Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities
Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities
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DOI：
10.1038/sj.cdd.4401704
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发表时间：
2006-01-01
影响因子：
12.4
通讯作者：
Ariga, H
中科院分区：
文献类型：
--
作者：
Shinbo, Y;Niki, T;Ariga, H
DJ-1是一种多功能蛋白，在转录调控和抗氧化应激中发挥作用，其功能的丧失被认为是导致帕金森病（PD）发病的原因。在这里，我们报告说，DJ-1是sumoylated赖氨酸残基在氨基酸编号130（K130）的PIASx α或PIASy。K130突变废除了DJ-1的所有功能，包括ras依赖性转化、细胞生长促进和抗UV诱导的凋亡活性。UV照射后DJ-1的类小泛素化增加，伴随着pI向DJ-1的酸性点的偏移。此外，在PD患者中发现的突变型DJ-1 L166 P和含有DJ-1中的四个突变的人工突变型K130 RX被不适当地sumoylated，并且它们变得不可溶，部分定位于线粒体中并被蛋白酶体系统降解。L166 P表达细胞和DJ-1敲低细胞都被发现对UV诱导的细胞凋亡高度敏感。
DJ-1 is a multifunctional protein that plays roles in transcriptional regulation and antioxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease (PD). Here, we report that DJ-1 was sumoylated on a lysine residue at amino-acid number 130 (K130) by PIASx alpha or PIASy. The K130 mutation abrogated all of the functions of DJ-1, including ras-dependent transformation, cell growth promotion and anti-UV-induced apoptosis activities. Sumoylation of DJ-1 was increased after UV irradiation concomitant with a pl shift to an acidic point of DJ-1. Furthermore, L166P, a mutant DJ-1 found in PD patients, and K130RX, an artificial mutant containing four mutations in DJ-1, were improperly sumoylated, and they became insoluble, partly localized in the mitochondria and degraded by the proteasome system. Both L166P-expressing cells and DJ-1-knockdown cells were found to be highly susceptible to UV-induced cell apoptosis.