title: RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function.
abstract: Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC) development. Hepatitis B virus X protein (HBx) is known to play a key role in the development of hepatocellular carcinoma (HCC). Several cellular proteins have been reported to be over-expressed in HBV-associated HCC tissues, but their role in the HBV-mediated oncogenesis remains largely unknown. Here, we explored the effect of the over-expressed cellular protein, a ribosomal protein S3a (RPS3a), on the HBx-induced NF-κB signaling as a critical step for HCC development. The enhancement of HBx-induced NF-κB signaling by RPS3a was investigated by its ability to translocate NF-κB (p65) into the nucleus and the knock-down analysis of RPS3a. Notably, further study revealed that the enhancement of NF-κB by RPS3a is mediated by its novel chaperoning activity toward physiological HBx. The over-expression of RPS3a significantly increased the solubility of highly aggregation-prone HBx. This chaperoning function of RPS3a for HBx is closely correlated with the enhanced NF-κB activity by RPS3a. In addition, the mutational study of RPS3a showed that its N-terminal domain (1-50 amino acids) is important for the chaperoning function and interaction with HBx. The results suggest that RPS3a, via extra-ribosomal chaperoning function for HBx, contributes to virally induced oncogenesis by enhancing HBx-induced NF-κB signaling pathway.
authors.affiliation: Department of Biotechnology, College of Life science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Keo-Heun
authors.initials: KH
authors.lastname: Lim
authors.forename: Kyun-Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Seong Il
authors.initials: SI
authors.lastname: Choi
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Park
authors.forename: Seung Hwa
authors.initials: SH
authors.lastname: Park
authors.forename: Kisun
authors.initials: K
authors.lastname: Ryu
authors.forename: Yong Kwang
authors.initials: YK
authors.lastname: Park
authors.forename: So Young
authors.initials: SY
authors.lastname: Kwon
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Yang
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Sung
authors.forename: Baik L
authors.initials: BL
authors.lastname: Seong
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D018832:Molecular Chaperones; D016328:NF-kappa B; C031016:RPS3A protein, human; D012269:Ribosomal Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D049452:Green Fluorescent Proteins