RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function

Keo Heun Lim, Kyun Hwan Kim, Seong Il Choi, Eun Sook Park, Seung Hwa Park, Kisun Ryu, Yong Kwang Park, So Young Kwon, Sung Il Yang, Han Chu Lee, In Kyung Sung, Baik Lin Seong

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Article numbere22258
JournalPLoS One
Volume6
Issue number8
DOIs
Publication statusPublished - 2011 Aug 19

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Hepatitis B virus
Ribosomal Proteins
ribosomal proteins
hepatoma
Viruses
Hepatocellular Carcinoma
carcinogenesis
Carcinogenesis
proteins
Virus Diseases
Solubility
solubility
Proteins
Agglomeration
Tissue
Amino Acids
amino acids

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lim, Keo Heun ; Kim, Kyun Hwan ; Choi, Seong Il ; Park, Eun Sook ; Park, Seung Hwa ; Ryu, Kisun ; Park, Yong Kwang ; Kwon, So Young ; Yang, Sung Il ; Lee, Han Chu ; Sung, In Kyung ; Seong, Baik Lin. / RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function. In: PLoS One. 2011 ; Vol. 6, No. 8.
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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.",
author = "Lim, {Keo Heun} and Kim, {Kyun Hwan} and Choi, {Seong Il} and Park, {Eun Sook} and Park, {Seung Hwa} and Kisun Ryu and Park, {Yong Kwang} and Kwon, {So Young} and Yang, {Sung Il} and Lee, {Han Chu} and Sung, {In Kyung} and Seong, {Baik Lin}",
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Lim, KH, Kim, KH, Choi, SI, Park, ES, Park, SH, Ryu, K, Park, YK, Kwon, SY, Yang, SI, Lee, HC, Sung, IK & Seong, BL 2011, 'RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function', PLoS One, vol. 6, no. 8, e22258. https://doi.org/10.1371/journal.pone.0022258

RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function. / Lim, Keo Heun; Kim, Kyun Hwan; Choi, Seong Il; Park, Eun Sook; Park, Seung Hwa; Ryu, Kisun; Park, Yong Kwang; Kwon, So Young; Yang, Sung Il; Lee, Han Chu; Sung, In Kyung; Seong, Baik Lin.

In: PLoS One, Vol. 6, No. 8, e22258, 19.08.2011.

Research output: Contribution to journalArticle

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T1 - RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function

AU - Lim, Keo Heun

AU - Kim, Kyun Hwan

AU - Choi, Seong Il

AU - Park, Eun Sook

AU - Park, Seung Hwa

AU - Ryu, Kisun

AU - Park, Yong Kwang

AU - Kwon, So Young

AU - Yang, Sung Il

AU - Lee, Han Chu

AU - Sung, In Kyung

AU - Seong, Baik Lin

PY - 2011/8/19

Y1 - 2011/8/19

N2 - 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.

AB - 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.

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