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.
Mesh Terms:
Apoptosis, Carrier Proteins, Cell Nucleus, Cells, Cultured, Humans, Hydrogen Peroxide, Intracellular Signaling Peptides and Proteins, Kidney, Mutation, Oncogene Proteins, Oxidative Stress, Protein Kinases, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Saccharomyces cerevisiae, Two-Hybrid System Techniques
Free Radic. Res.
Date: Feb. 01, 2006
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