Zfra is an inhibitor of Bcl-2 expression and cytochrome c release from the mitochondria

Li Jin Hsu, Qunying Hong, Lori Schultz, Emory Kuo, Sing Ru Lin, Ming Hui Lee, Yee Shin Lin, Nan Shan Chang

研究成果: Article

14 引文 斯高帕斯(Scopus)

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-κB) 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.

原文English
頁(從 - 到)1303-1312
頁數10
期刊Cellular Signalling
20
發行號7
DOIs
出版狀態Published - 2008 七月 1

All Science Journal Classification (ASJC) codes

  • Cell Biology

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