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

Anna Alisi, Stefania Giambartolomei, Felicia Cupelli, Paola Merlo, Giulia Fontemaggi, Alessandra Spaziani, Clara Balsano

Research output: Contribution to journalArticlepeer-review

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 coimmunoprecipitated 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.

Original languageEnglish
Pages (from-to)2573-2580
Number of pages8
JournalOncogene
Volume22
Issue number17
DOIs
Publication statusPublished - May 1 2003

Keywords

  • Core p53
  • HCC
  • HCV
  • p21
  • p73

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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