%0 Journal Article
%T RPS3a Over-Expressed in HBV-Associated Hepatocellular Carcinoma Enhances the HBx-Induced NF-百B Signaling via Its Novel Chaperoning Function
%A Keo-Heun Lim
%A Kyun-Hwan Kim
%A Seong Il Choi
%A Eun-Sook Park
%A Seung Hwa Park
%A Kisun Ryu
%A Yong Kwang Park
%A So Young Kwon
%A Sung-Il Yang
%A Han Chu Lee
%A In-Kyung Sung
%A Baik L. Seong
%J PLOS ONE
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0022258
%X 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-百B signaling as a critical step for HCC development. The enhancement of HBx-induced NF-百B signaling by RPS3a was investigated by its ability to translocate NF-百B (p65) into the nucleus and the knock-down analysis of RPS3a. Notably, further study revealed that the enhancement of NF-百B 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-百B activity by RPS3a. In addition, the mutational study of RPS3a showed that its N-terminal domain (1每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-百B signaling pathway.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022258