PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death.
Jing TangJinghua LiuXue LiYuyun ZhongTian-Yu ZhongYawei LiuJiang Huai WangYong JiangPublished in: Oxidative medicine and cellular longevity (2014)
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.
Keyphrases
- cell cycle arrest
- cell death
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- protein kinase
- signaling pathway
- pi k akt
- transcription factor
- binding protein
- electronic health record
- human immunodeficiency virus
- artificial intelligence
- deep learning
- hepatitis c virus
- protein protein
- heat shock protein