PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death.
PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death.
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PRAK 与 DJ-1 相互作用并防止氧化应激诱导的细胞死亡
DOI：
10.1155/2014/735618
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发表时间：
2014
影响因子：
--
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Tang J;Liu J;Li X;Zhong Y;Zhong T;Liu Y;Wang JH;Jiang Y
p38调节/活化激酶（p38 regulated/activated kinase， PRAK）作为p38 MAPK信号转导通路的核心成员，被细胞应激激活。然而，PRAK及其下游相互作用伙伴的功能仍不明确。利用酵母双杂交系统，我们确定了DJ-1是一个潜在的PRAK相互作用蛋白。我们进一步在体外和体内验证了DJ-1与PRAK结合，并在NIH3T3细胞的细胞核中与PRAK共定位。此外，在H2O2刺激下，PRAK+/+细胞中的大多数内源性DJ-1仍然留在细胞核中，而PRAK - / -细胞中的大多数DJ-1从细胞核转移到细胞质中，这表明PRAK是DJ-1定位于细胞核所必需的。此外，在体外和体内h2o2激发的PRAK+/+细胞中观察到DJ-1与PRAK相关的磷酸化。在h2o2处理的PRAK - / -细胞中，DJ-1的细胞质易位失去了在细胞核中隔离Daxx（一种死亡蛋白）的能力，结果Daxx进入细胞质并引发细胞死亡。这些数据表明，DJ-1是PRAK的下游相互作用靶点，在氧化应激反应中，PRAK可能通过促进DJ-1将Daxx隔离在细胞核中，从而起到细胞保护作用，从而防止细胞死亡。
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.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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作者：
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10.1152/ajpheart.1999.277.5.h2026
发表时间：
1999-11-01
影响因子：
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通讯作者：
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影响因子：
50.3
作者：
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