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

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 interactin...

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Detalles Bibliográficos
Autores principales: Tang, Jing, Liu, Jinghua, Li, Xue, Zhong, Yuyun, Zhong, Tianyu, Liu, Yawei, Wang, Jiang Huai, Jiang, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212658/
https://www.ncbi.nlm.nih.gov/pubmed/25383140
http://dx.doi.org/10.1155/2014/735618
Descripción
Sumario: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 H(2)O(2) 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 H(2)O(2)-challenged PRAK(+/+) cells. Cytoplasmic translocation of DJ-1 in H(2)O(2)-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.