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首页> 外文期刊>Cellular Signalling >Zfra is an inhibitor of Bcl-2 expression and cytochrome c release from the mitochondria
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Zfra is an inhibitor of Bcl-2 expression and cytochrome c release from the mitochondria

机译：Zfra是线粒体中Bcl-2表达和细胞色素c释放的抑制剂

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摘要

Zfra is a small size 31-amino-acid C2H2 zinc finger-like protein, which is known to interact with c-Jun N-terminal kinase 1 (JNK1), WW domain-containing oxidoreductase (WWOX, FOR or WOX1), TNF receptor-associated death domain protein (TRADD) and nuclear factor kappaB (NF-kappa B) during stress response. Here, we show that Zfra became phosphorylated at Ser8 (as determined by specific antibody) and translocated to the mitochondria in response to inducers of mitochondrial permeability transition (MPT) (e.g. staurosporine and betulinic acid). Overexpressed Zfra induced cell death. This event is associated, in part, with increased dissipation of mitochondrial membrane potential (MMP) and increased chromosomal DNA fragmentation. Intriguingly, Zfra significantly downregulated Bcl-2 and yet blocked cytochrome c release from the mitochondria. Overexpression of an S8G-Zfra mutant (Ser8 to Gly8 alteration) could not induce cell death, probably due to its failure of translocating to the mitochondria and causing MMP dissipation. Over-expressed proapoptotic WOX1 induced cytochrome c release from the mitochondria. Zfra bound and blocked the effect of WOX1. Taken together, Ser8 is essential for overexpressed Zfra to exert cell death via the mitochondrial pathway. Zfra downregulates Bcl-2 and induces MMP dissipation but causes no cytochrome c release, indicating a novel death pathway from the mitochondria. (c) 2008 Elsevier Inc. All rights reserved.
机译：Zfra是小巧的31个氨基酸的C2H2锌指状蛋白，已知与c-Jun N端激酶1（JNK1），含WW域的氧化还原酶（WWOX，FOR或WOX1），TNF受体相互作用应激反应过程中相关的死亡域蛋白（TRADD）和核因子κB（NF-κB）。在这里，我们显示Zfra在Ser8处被磷酸化（由特异性抗体确定），并响应线粒体通透性转变（MPT）的诱导物（例如星形孢菌素和桦木酸）而转位至线粒体。过表达的Zfra诱导细胞死亡。此事件部分与线粒体膜电位（MMP）耗散增加和染色体DNA片段化增加有关。有趣的是，Zfra显着下调了Bcl-2，但阻止了细胞色素c从线粒体释放。 S8G-Zfra突变体（Ser8到Gly8的改变）的过表达不能诱导细胞死亡，这可能是由于其无法转运到线粒体并导致MMP耗散。过表达的促凋亡WOX1诱导线粒体细胞色素c的释放。 Zfra绑定并阻止了WOX1的作用。总之，Ser8对于过表达的Zfra通过线粒体途径发挥细胞死亡至关重要。 Zfra下调Bcl-2，诱导MMP耗散，但不引起细胞色素c释放，表明线粒体有新的死亡途径。 （c）2008 Elsevier Inc.保留所有权利。

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