Physical and functional interaction between HCV core protein and the different p73 isoforms.
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 p21(WAF1/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 alpha or p73 beta tumor-suppressor proteins. In addition, the interaction with HCV core protein prevents p73 alpha, but not p73 beta 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.
Fondazione Andrea Cesalpino, I Clinica Medica, V.le del Policlinico 155, 00161 Roma, Italy.
Anna
A
Alisi
Stefania
S
Giambartolomei
Felicia
F
Cupelli
Paola
P
Merlo
Giulia
G
Fontemaggi
Alessandra
A
Spaziani
Clara
C
Balsano
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D066298:In Vitro Techniques; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D014758:Viral Core Proteins / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus