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http://dx.doi.org/10.4014/jmb.1012.12023

RKIP Downregulation Induces the HBx-Mediated Raf-1 Mitochondrial Translocation  

Kim, Sun-Young (Medical Proteomics Research Center, KRIBB)
Park, Sung-Goo (Medical Proteomics Research Center, KRIBB)
Jung, Hye-Yun (Medical Proteomics Research Center, KRIBB)
Chi, Seung-Wook (Medical Proteomics Research Center, KRIBB)
Yu, Dae-Yeul (Ageing Research Center, KRIBB)
Lee, Sang-Chul (Medical Proteomics Research Center, KRIBB)
Bae, Kwang-Hee (Medical Proteomics Research Center, KRIBB)
Publication Information
Journal of Microbiology and Biotechnology / v.21, no.5, 2011 , pp. 525-528 More about this Journal
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.
Keywords
Hepatitis B virus X; hepatocarcinogenesis; Raf-1; RKIP;
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