DJ-1 interacts with HIPK1 and affects H2O2-induced cell death
DJ-1 interacts with HIPK1 and affects H2O2-induced cell death
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DOI：
10.1080/10715760500456847
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发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Ariga, H
中科院分区：
文献类型：
--
作者：
Sekito, A;Koide-Yoshida, S;Ariga, H
DJ-1是一种新的癌基因，也是家族性帕金森病（PD）的致病基因。DJ-1具有多种功能，包括通过消除活性氧（ROS）和作为共激活因子的转录调节来抗氧化应激，并且这些功能的丧失被认为触发PD的发作。然而，DJ-1预防细胞死亡的机制尚不清楚。在本研究中，我们发现DJ-1直接结合同源域相互作用蛋白激酶1（HIPK 1）在体外和体内，这些蛋白是共定位在细胞核中。然后发现HIPK 1在用野生型DJ-1转染但用C106 S DJ-1突变体转染的人H1299细胞中以剂量依赖性方式降解，C106 S DJ-1突变体是一种破坏推定蛋白酶催化结构域的DJ-1蛋白。此外，尽管DJ-1或HIPK 1的敲低使H1299细胞对H2 O2诱导的细胞死亡敏感，但DJ-1和HIPK 1的双敲低使H1299细胞对H2 O2诱导的细胞死亡具有抗性，这表明由低水平的DJ-1诱导的HIPK 1水平升高抑制了氧化应激诱导的细胞死亡。
DJ-1 is a novel oncogene and causative gene for the familial form of Parkinson's disease (PD). DJ-1 has multiple functions, including anti-oxidative stress by eliminating reactive oxygen species (ROS) and transcriptional regulation as a coactivator, and loss of these functions are thought to trigger the onset of PD. The mechanism underlying the prevention of cell death by DJ-1 is, however, not clear. In this study, we found that DJ-1 directly bound to homeodomaininteracting protein kinase 1 (HIPK1) in vitro and in vivo and that these proteins were colocalized in the nucleus. HIPK1 was then found to be degraded in human H1299 cells transfected with wild-type DJ-1 but not with a C106S DJ-1 mutant, a DJ-1 protein disrupting a catalytic domain of the putative protease, in a dose-dependent manner. Furthermore, although knockdown of either DJ-1 or HIPK1 rendered H1299 cells susceptible to H2O2-induced cell death, double-knockdown of DJ-1 and HIPK1 rendered H1299 cells resistant to H2O2-induced cell death, suggesting that the elevated level of HIPK1 induced by a low level of DJ-1 inhibits oxidative stress-induced cell death.