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KMID : 0545120110210050525
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Journal of Microbiology and Biotechnology
2011 Volume.21 No. 5 p.525 ~ p.528
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RKIP Downregulation Induces the HBx-Mediated Raf-1 Mitochondrial Translocation
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Kim Sun-Young
Park Sung-Goo
Jung Hyeyun
Chi Seung-Wook
Yu Dae-Yeul
Lee Sang-Chul
Bae Kwang-Hee
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Abstract
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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.
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KEYWORD
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Hepatitis B virus X, Hepatocarcinogenesis, Raf-1, RKIP
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