1. DJ-1 interacts with HIPK1 and affects H2O2-induced cell death
- Author
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Takahiro Taira, Hiroyoshi Ariga, Sanae M.M. Iguchi-Ariga, Aya Sekito, Takeshi Niki, and Shizuyo Koide-Yoshida
- Subjects
Programmed cell death ,Mutant ,Protein Deglycase DJ-1 ,Apoptosis ,Saccharomyces cerevisiae ,Biology ,Protein Serine-Threonine Kinases ,Kidney ,Biochemistry ,Two-Hybrid System Techniques ,Coactivator ,Transcriptional regulation ,Humans ,RNA, Small Interfering ,Protein kinase A ,Cells, Cultured ,Cell Nucleus ,Oncogene Proteins ,Gene knockdown ,Oncogene ,Reverse Transcriptase Polymerase Chain Reaction ,Intracellular Signaling Peptides and Proteins ,General Medicine ,Transfection ,Hydrogen Peroxide ,Molecular biology ,Cell biology ,Oxidative Stress ,Mutation ,Carrier Proteins ,Protein Kinases - Abstract
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.
- Published
- 2006