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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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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. |
format | Online Article Text |
id | pubmed-4212658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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