title: RKIP downregulation induces the HBx-mediated Raf-1 mitochondrial translocation.
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.
authors: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnlogy, Daejeon, Korea.
authors: Sun Young
authors: SY
authors: Kim
authors: Sung Goo
authors: SG
authors: Park
authors: Hyeyun
authors: H
authors: Jung
authors: Seung-Wook
authors: SW
authors: Chi
authors: Dae Yeul
authors: DY
authors: Yu
authors: Sang Chul
authors: SC
authors: Lee
authors: Kwang-Hee
authors: KH
authors: Bae