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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Balint E, Bates S and Vousden KH . (1999). Oncogene, 18, 3923–3929.
Barba G, Harper F, Harada T, Kohara M, Goulinet S, Matsuura Y, Eder G, Schaff ZS, Chapman MJ, Myamura T and Brechot C . (1997). Proc. Natl. Acad. Sci. USA, 94, 1200–1205.
Basu A, Meyer K, Ray RB and Ray R . (2002). Virology, 298, 53–62.
Colombo M . (1999). J. Hepatol., 31(Suppl 1), 25–30.
Costanzo A, Merlo P, Pediconi N, Fulco M, Sartorelli V, Cole PA, Fontemaggi G, Fanciulli M, Schiltz L, Blandino G, Balsano C and Levrero M . (2002). Mol. Cell, 9, 175–186.
De Francesco R . (1999). J. Hepatol., 31, 47–53.
De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annichiarico-Petruzzeli M, Levrero M and Melino G . (1998). J. Exp. Med., 188, 1763–1768.
Giambartolomei S, Covone F, Levrero M and Balsano C . (2001). Oncogene, 20, 2606–2610.
Hayashi J, Aoki H, Arakawa Y and Hino O . (1999). Intervirology, 42, 205–210.
Higashino F, Pipas JM and Shenk T . (1998). Proc. Natl. Acad. Sci. USA, 95, 15683–15687.
Jin DY, Wang HL, Zhou Y, Chun AC, Kibler KV, Hou YD, Kung H and Jeang KT . (2000). EMBO J., 19, 729–740.
Jost CA, Marin MC and Kaelin Jr WG . (1997). Nature, 389, 191–194.
Kaghad M, Bonnet H, Yang I, Creancier J, Biscan C, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, Me Keon F and Caput D . (1997). Cell, 90, 809–819.
Kaida A, Ariumi Y, Ueda Y, Lin JY, Hijikata M, Ikawa S and Shimotono K . (2000). Oncogene, 19, 827–830.
Koike K, Tsutsumi T, Fujie H, Shintani Y and Moriya K . (2002). Oncology, 62, 29–37.
Levrero M, De Laurenzi V, Costanzo A, Gong J, Melino G and Wang JYJ . (1999). Cell Death Differ., 6, 1146–1153.
Lu W, Lo S, Chen M, Wu K, Fung YK and Ou J . (1999). Virology, 264, 134–141.
Maillard P, Krawczynski K, Nitkiewicz J, Bronnert C, Sidorkiewicz M, Gounon P, Dubuisson J, Faure G, Crainic R and Budkowska A . (2001). J. Virol., 75, 8240–8250.
Mamiya N and Worman HJ . (1999). J. Biol. Chem., 274, 15751–15756.
Marusawa H, Hijikata M, Chiba T and Shimotono K . (1999). J. Virol., 73, 4713–4720.
Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T and Koike K . (1998). Nat. Med., 9, 1065–1067.
Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, Miyamura T and Koike K . (1997). J. Gen. Virol., 78, 1527–1531.
Otsuka M, Kato N, Lan KH, Yoshida H, Kato J, Goto T, Shiratori Y and Omata M . (2000). J. Biol. Chem., 275, 34122–34130.
Park KJ, Choi SH, Lee SY, Hwang SB and Lai MMC . (2002). J. Biol. Chem., 277, 13122–13128.
Prabhu NS, Somasundaram K, Satyamoorthy K, Herlyn M and El-Deiry WS . (1998). Int. J. Oncol., 13, 5–9.
Ray RB, Meyer K and Ray R . (1996). Virology, 226, 176–182.
Ray RB, Meyer K and Ray R . (2000). Virology, 271, 197–204.
Ray RB, Steel R, Meyer K and Ray R . (1998). Gene, 208, 331–336.
Reichelt M, Zang KD, Seifart M, Welter C and Ruffing T . (1999). Arch. Virol., 144, 621–626.
Serrano M, Lin AW, Mc Currach ME, Beach D and Lowe SW . (1997). Cell, 88, 593–602.
Sherr CJ and Roberts JM . (1999). Genes Dev., 13, 1501–1512.
Shi ST, Polyak SJ, Tu H, Taylor DR, Gretch DR and Lai MM . (2002). Virology, 292, 198–210.
Stiewe T, Theseling CC and Putzer BM . (2002). J. Biol. Chem., 277, 14177–14185.
Takamatsu M, Fujita T and Hotta H . (2001). Kobe J. Med. Sci., 47, 97–112.
Tannapfel A, Wasner M, Krause K, Geissler F, Katalinic A, Hauss J, Mossner J, Engeland K and Wittekind C . (1999). J. Natl. Cancer, 79, 164–167.
Thompson EB . (1998). Annu. Rev. Physiol., 60, 575–600.
Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K and Miyamura T . (2002). Hepatology, 35, 937–946.
Uchida M, Hino N, Yamanaka T, Fukushima H, Imanishi T, Uchiyama Y, Kodama T and Doi T . (2002). Hepatol. Res., 22, 297–306.
Vossio S, Palescandolo E, Pediconi N, Moretti F, Balsano C, Levrero M and Costanzo A . (2002). Oncogene, 21, 3796–3803.
Wienzek S, Roth J and Dobbelstein M . (2000). J. Virol., 74, 193–202.
Yamanaka T, Kodama T and Doi T . (2002). Biochem. Biophys. Res. Commun., 294, 528–534.
You L, Chen C, Yeh T, Tsai T, Mai R, Lin C and Lee Y . (1999). J. Virol., 73, 2841–2853.
Zemel R, Koren C, Bachmatove L, Avigad S, Kaganovsky E, Okon E, Ben-Ari Z, Brief F, Ben-Yehoyada M, Shaul Y and Tur-kaspa R . (2002). Dig. Dis. Sci., 47, 716–722.
Zeng YX and Eiry WS . (1996). Oncogene, 12, 1557–1564.
Zhu N, Khoshan A, Schneider R, Matsumoto M, Denner G, Ware C and Lai MMC . (1998). J. Virol., 72, 3691–3697.
Acknowledgements
This work was supported by a grant from AIRC and Schering-Plough. Anna Alisi was supported by fellowship from Fondazione A Cesalpino.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1038/sj.onc.1206333
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1206333
Keywords
This article is cited by
-
Chronic Hepatitis C Virus Infection is Associated with an Increased Risk of Lung Cancer: A Systematic Review and Meta-analysis
Lung (2020)
-
Impact of IL28 Genotypes and Modeling the Interactions of HCV Core Protein on Treatment of Hepatitis C
Interdisciplinary Sciences: Computational Life Sciences (2020)
-
Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview
Journal of Translational Medicine (2011)
-
Viral hepatocarcinogenesis
Oncogene (2010)
-
Viral hepatitis and liver cancer: the case of hepatitis C
Oncogene (2006)