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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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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
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author Tang, Jing
Liu, Jinghua
Li, Xue
Zhong, Yuyun
Zhong, Tianyu
Liu, Yawei
Wang, Jiang Huai
Jiang, Yong
author_facet Tang, Jing
Liu, Jinghua
Li, Xue
Zhong, Yuyun
Zhong, Tianyu
Liu, Yawei
Wang, Jiang Huai
Jiang, Yong
author_sort Tang, Jing
collection PubMed
description 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.
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spelling pubmed-42126582014-11-09 PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death Tang, Jing Liu, Jinghua Li, Xue Zhong, Yuyun Zhong, Tianyu Liu, Yawei Wang, Jiang Huai Jiang, Yong Oxid Med Cell Longev Research Article 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. Hindawi Publishing Corporation 2014 2014-10-14 /pmc/articles/PMC4212658/ /pubmed/25383140 http://dx.doi.org/10.1155/2014/735618 Text en Copyright © 2014 Jing Tang et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Tang, Jing
Liu, Jinghua
Li, Xue
Zhong, Yuyun
Zhong, Tianyu
Liu, Yawei
Wang, Jiang Huai
Jiang, Yong
PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death
title PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death
title_full PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death
title_fullStr PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death
title_full_unstemmed PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death
title_short PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death
title_sort prak interacts with dj-1 and prevents oxidative stress-induced cell death
topic Research Article
url 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
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