RKIP downregulation induces the HBx-mediated Raf-1 mitochndrial translocation

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Title
RKIP downregulation induces the HBx-mediated Raf-1 mitochndrial translocation
Author(s)
Sun Young Kim; Sung Goo Park; Hyeyun Jung; Seung-Wook Chi; Dae Yeul Yu; Sang Chul LeeKwang-Hee Bae
Bibliographic Citation
Journal of Microbiology and Biotechnology, vol. 21, no. 5, pp. 525-528
Publication Year
2011
Abstract
The Raf-1 kinase inhibitory protein (RKIP) can regulate multiple key signaling pathways. Specifically, RKIP binds to Raf-1 kinase and inhibits the Ras-Raf-1-MEK1/2-ERK1/2 pathway. Additionally, Raf-1 has been shown to translocate to mitochondria and thereby protect cells from stress-mediated apoptosis. Recently, HBx was found to stimulate the mitochondrial translocation of Raf-1, contributing to the anti-apoptotic effect. We found that RKIP was downregulated during HBx-mediated hepatocarcinogenesis. In this study, we show that RKIP bound to Raf-1 and consequently inhibited the translocation of Raf-1 into mitochondria. This promoted the apoptosis of cells treated with apoptotic stimulus. Thus, the downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis. The elevated Raf-1 mitochondrial translocation induced the increased anti-apoptotic effect and subsequently promoted HBx-mediated hepatocarcinogenesis.
Keyword
Hepatitis B virus XHepatocarcinogenesisRaf-1RKIP
ISSN
1017-7825
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.4014/jmb.1012.12023
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Biomedical Research > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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