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

被引:51
作者
Alisi, A
Giambartolomei, S
Cupelli, F
Merlo, P
Fontemaggi, G
Spaziani, A
Balsano, C
机构
[1] Fdn Andrea Cesalpino, Med Clin 1, I-00161 Rome, Italy
[2] Univ Aquila, Dip MISP, I-67100 Laquila, Italy
[3] Regina Elena Inst Canc Res, I-00158 Rome, Italy
关键词
HCV; core p53; p73; p21(WAF1/CIP1); HCC;
D O I
10.1038/sj.onc.1206333
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 or 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.
引用
收藏
页码:2573 / 2580
页数:8
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