Physical and functional interaction between HCV core protein and the different p73 isoforms

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Abstract

Hepatitis C virus (HCV) core protein is a structural viral protein that packages the viral genomic RNA. In addition to this function, HCV core also modulates a number of cellular regulatory functions. In fact, HCV core protein has been found to modulate the expression of the cyclin-dependent inhibitor p21WAF1/CIP1 and to promote both apoptosis and cell proliferation through its physical interaction with p53. Here, we studied the ability of HCV core to bind the p53-related p73 protein, its isoforms and its deletion mutants. We found that HCV core co-immunoprecipitated with p73 in HepG2 and SAOS-2 cells. Deletion mutational analysis of p73 indicates that the domain involved in HCV core binding is located between amino-acid residues 321–353. We also demonstrate that p73/core interaction results in the nuclear translocation of HCV core protein either in the presence of the p73 α or p73 β tumor-suppressor proteins. In addition, the interaction with HCV core protein prevents p73 α, but not p73 β dependent cell growth arrest in a p53-dependent manner. Our findings demonstrate that HCV core protein may directly influence the various p73 functions, thus playing a role in HCV pathogenesis.

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Acknowledgements

This work was supported by a grant from AIRC and Schering-Plough. Anna Alisi was supported by fellowship from Fondazione A Cesalpino.

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Correspondence to Clara Balsano.

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Alisi, A., Giambartolomei, S., Cupelli, F. et al. Physical and functional interaction between HCV core protein and the different p73 isoforms. Oncogene 22, 2573–2580 (2003) doi:10.1038/sj.onc.1206333

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Keywords

  • HCV
  • core p53
  • p73
  • p21WAF1/CIP1
  • HCC

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