Specific cleavage of DJ-1 under an oxidative condition
Specific cleavage of DJ-1 under an oxidative condition
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DOI：
10.1016/j.neulet.2006.06.067
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发表时间：
2006-10-09
影响因子：
2.5
通讯作者：
Ariga, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Ooe, Hiromasa;Maita, Chinatsu;Ariga, Hiroyoshi
DJ-1最初被我们鉴定为一个新的癌基因，最近被发现是家族性帕金森病（PD）PARK 7的致病基因。DJ-1在转录调节和氧化应激功能中发挥作用，其半胱氨酸残基的氧化状态决定了DJ-1的活性。本研究中，我们发现重组DJ-1在大肠杆菌中表达并纯化。大肠杆菌中，通过用H2 O2处理DJ-1，分别在氨基酸编号157和158处的甘氨酸和脯氨酸之间特异性切割。在DJ-1的主要氧化位点106号氨基酸处，发现DJ-1从半胱氨酸到丝氨酸的取代突变体在氧化条件下不被切割，表明DJ-1的氧化依赖性切割。在用H2 O2处理的人SH-SY 5 Y细胞中也观察到DJ-1的裂解。这些结果表明，氧化应激诱导的DJ-1裂解调节DJ-1的功能。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
DJ-1 was initially identified by us as a novel oncogene and has recently been found to be a causative gene for familial Parkinon's disease (PD) PARK7. DJ-1 plays roles in transcriptional regulation and in oxidative stress function, and its oxidative state at cysteine residues determines activities of DJ-1. In this study, we found that recombinant DJ-1 expressed in and purified from E. coli was specifically cleaved between glycine and proline at amino acid numbers 157 and 158, respectively, by treatment of DJ-1 with H2O2. A substitution mutant of DJ-1 from cysteine to serine at amino acid number 106, a major oxidation site of DJ-1, was found not to be cleaved under an oxidative condition, suggesting oxidation-dependent cleavage of DJ-1. Cleavage of DJ-1 was also observed in human SH-SY5Y cells that had been treated with H2O2. These results suggest that oxidative stress-induced cleavage of DJ-1 regulates functions of DJ-1. (c) 2006 Elsevier Ireland Ltd. All rights reserved.