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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Main Authors:	Tang, Jing, Liu, Jinghua, Li, Xue, Zhong, Yuyun, Zhong, Tianyu, Liu, Yawei, Wang, Jiang Huai, Jiang, Yong
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212658/

id	pubmed-4212658
recordtype	oai_dc
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 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 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. 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Tang, Jing Liu, Jinghua Li, Xue Zhong, Yuyun Zhong, Tianyu Liu, Yawei Wang, Jiang Huai Jiang, Yong
spellingShingle	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
author_facet	Tang, Jing Liu, Jinghua Li, Xue Zhong, Yuyun Zhong, Tianyu Liu, Yawei Wang, Jiang Huai Jiang, Yong
author_sort	Tang, Jing
title	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_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_sort	prak interacts with dj-1 and prevents oxidative stress-induced cell death
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 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.
publisher	Hindawi Publishing Corporation
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212658/
_version_	1613149920296960000

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

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