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

• Published in: Journal of microbiology and biotechnology Vol. 21; no. 5; pp. 525 - 528
• Main Authors: Kim, S.Y., Medical Proteomics Research Center, KRIBB, Daejeon, Republic of Korea, Park, S.G., Medical Proteomics Research Center, KRIBB, Daejeon, Republic of Korea, Jung, H.Y., Medical Proteomics Research Center, KRIBB, Daejeon, Republic of Korea, Chi, S.W., Medical Proteomics Research Center, KRIBB, Daejeon, Republic of Korea, Yu, D.Y., Ageing Research Center, KRIBB, Daejeon, Republic of Korea, Lee, S.C., Medical Proteomics Research Center, KRIBB, Daejeon, Republic of Korea, Bae, K.H., Medical Proteomics Research Center, KRIBB, Daejeon, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Seoul Korean Society for Applied Microbiology 01.05.2011; 한국미생물·생명공학회
• Subjects: Biological and medical sciences; Biotechnology; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Cell Line, Tumor; CELLS; CELLULE; CELULAS; Down-Regulation; Fundamental and applied biological sciences. Psychology; Hepatitis B virus - genetics; Hepatitis B virus - metabolism; Hepatitis B virus X; hepatocarcinogenesis; Humans; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - virology; Mitochondria - enzymology; Mitochondria - genetics; Phosphatidylethanolamine Binding Protein - genetics; Phosphatidylethanolamine Binding Protein - metabolism; Protein Transport; Proto-Oncogene Proteins c-raf - genetics; Proto-Oncogene Proteins c-raf - metabolism; Raf-1; RKIP; Trans-Activators - genetics; Trans-Activators - metabolism; 생물학; Virus; Translocation; Liver cancer; Hepadnaviridae; RKIP; Orthohepadnavirus; Raf-1; Hepatitis B virus; hepatocarcinogenesis; Hepatitis B virus X
• ISSN: 1017-7825; 1738-8872
• DOI: 10.4014/jmb.1012.12023

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.