DJ-1 interacts with HIPK1 and affects H2O2-induced cell death.
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.
Sekito
Aya
A
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
Koide-Yoshida
Shizuyo
S
Niki
Takeshi
T
Taira
Takahiro
T
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology; D009154:Mutation; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D011494:Protein Kinases; C115113:Hipk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1