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Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis.
Oncogene. 2001 Jun 21; 20(28):3620-8.O

Abstract

Chronic hepatitis B virus (HBV) infection and the integration of its X gene (HBx) are closely associated with the development of hepatocellular carcinoma (HCC). The integrated HBx frequently is truncated or contains point mutations. Previous studies indicated that these HBx mutants have a diminished co-transactivational activity. We have compared the effects of wild-type (wt) HBx and its naturally occurring mutants derived from human HCCs on transcriptional co-transactivation, apoptosis and interactive effects with p53. We demonstrated that overexpression of mutant, but not wt HBx, is defective in transcriptional co-transactivation of the NF-kappaB-driven luciferase reporter. By using a microinjection technique, the HBx mutants were shown to have an attenuated pro-apoptotic activity. This deficiency may be attributed to multiple mutations in the co-transactivation domain of HBx, that leads to decreased stability of the translated product. However, wt or mutant HBx bind to p53 in vitro and retain their ability to block p53-mediated apoptosis in vivo, which has been implicated as its major tumor suppressor function. The abrogation of p53-mediated apoptosis by integrated HBx mutants may provide a selective clonal advantage for preneoplastic or neoplastic hepatocytes and contribute to hepatocellular carcinogenesis.

Authors+Show Affiliations

Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892 USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11439325

Citation

Huo, T I., et al. "Hepatitis B Virus X Mutants Derived From Human Hepatocellular Carcinoma Retain the Ability to Abrogate P53-induced Apoptosis." Oncogene, vol. 20, no. 28, 2001, pp. 3620-8.
Huo TI, Wang XW, Forgues M, et al. Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. Oncogene. 2001;20(28):3620-8.
Huo, T. I., Wang, X. W., Forgues, M., Wu, C. G., Spillare, E. A., Giannini, C., Brechot, C., & Harris, C. C. (2001). Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. Oncogene, 20(28), 3620-8.
Huo TI, et al. Hepatitis B Virus X Mutants Derived From Human Hepatocellular Carcinoma Retain the Ability to Abrogate P53-induced Apoptosis. Oncogene. 2001 Jun 21;20(28):3620-8. PubMed PMID: 11439325.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. AU - Huo,T I, AU - Wang,X W, AU - Forgues,M, AU - Wu,C G, AU - Spillare,E A, AU - Giannini,C, AU - Brechot,C, AU - Harris,C C, PY - 2000/12/05/received PY - 2001/03/21/revised PY - 2001/04/02/accepted PY - 2001/7/6/pubmed PY - 2001/8/3/medline PY - 2001/7/6/entrez SP - 3620 EP - 8 JF - Oncogene JO - Oncogene VL - 20 IS - 28 N2 - Chronic hepatitis B virus (HBV) infection and the integration of its X gene (HBx) are closely associated with the development of hepatocellular carcinoma (HCC). The integrated HBx frequently is truncated or contains point mutations. Previous studies indicated that these HBx mutants have a diminished co-transactivational activity. We have compared the effects of wild-type (wt) HBx and its naturally occurring mutants derived from human HCCs on transcriptional co-transactivation, apoptosis and interactive effects with p53. We demonstrated that overexpression of mutant, but not wt HBx, is defective in transcriptional co-transactivation of the NF-kappaB-driven luciferase reporter. By using a microinjection technique, the HBx mutants were shown to have an attenuated pro-apoptotic activity. This deficiency may be attributed to multiple mutations in the co-transactivation domain of HBx, that leads to decreased stability of the translated product. However, wt or mutant HBx bind to p53 in vitro and retain their ability to block p53-mediated apoptosis in vivo, which has been implicated as its major tumor suppressor function. The abrogation of p53-mediated apoptosis by integrated HBx mutants may provide a selective clonal advantage for preneoplastic or neoplastic hepatocytes and contribute to hepatocellular carcinogenesis. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11439325/Hepatitis_B_virus_X_mutants_derived_from_human_hepatocellular_carcinoma_retain_the_ability_to_abrogate_p53_induced_apoptosis_ L2 - http://dx.doi.org/10.1038/sj.onc.1204495 DB - PRIME DP - Unbound Medicine ER -