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Oxidative Medicine and Cellular Longevity
Volume 2014, Article ID 735618, 13 pages
http://dx.doi.org/10.1155/2014/735618
Research Article

PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death

1State Key Laboratory of Organ Failure Research, Key Laboratory of Transcriptomics and Proteomics, Ministry of Education of China, Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou 510515, China
2Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
3Department of Surgery, Cork University Hospital, University College Cork, Cork, Ireland

Received 23 May 2014; Accepted 27 August 2014; Published 14 October 2014

Academic Editor: Ozcan Erel

Copyright © 2014 Jing Tang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

As a core member of p38 MAPK signal transduction pathway, p38 regulated/activated kinase (PRAK) is activated by cellular stresses. However, the function of PRAK and its downstream interacting partner remain undefined. Using a yeast two-hybrid system, we identified DJ-1 as a potential PRAK interacting protein. We further verified that DJ-1 bound to PRAK in vitro and in vivo and colocalized with PRAK in the nuclei of NIH3T3 cells. Furthermore, following H2O2 stimulation the majority of endogenous DJ-1 in PRAK+/+ cells still remained in the nucleus, whereas most DJ-1 in PRAK−/− cells translocated from the nucleus into the cytoplasm, indicating that PRAK is essential for DJ-1 to localize in the nucleus. In addition, PRAK-associated phosphorylation of DJ-1 was observed in vitro and in vivo of H2O2-challenged PRAK+/+ cells. Cytoplasmic translocation of DJ-1 in H2O2-treated PRAK−/− cells lost its ability to sequester Daxx, a death protein, in the nucleus, and as a result, Daxx gained access to the cytoplasm and triggered cell death. These data highlight that DJ-1 is the downstream interacting target for PRAK, and in response to oxidative stress PRAK may exert a cytoprotective effect by facilitating DJ-1 to sequester Daxx in the nucleus, thus preventing cell death.