P53-dependent transcriptional repression of p21waf1 by hepatitis C virus NS3

Hyun Jin Kwun, E. Y. Jung, J. Y. Ahn, M. N. Lee, K. L. Jang

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) NS3 protein is known to affect normal cellular functions, such as cell proliferation and cell death, and to be involved, either directly or indirectly, in HCV hepatocarcinogenesis. In this study, we demonstrated that NS3 protein could specifically repress the promoter activity of p21 in a dose-dependent manner. The effect was not cell type-specific and was synergistic when combined with HCV core protein. Repression of the p21 promoter by NS3 was almost completely lost when p53 binding sites present on the p21 promoter were removed. Furthermore, p53 binding sites were sufficient to confer a strong NS3 responsiveness to an heterologous promoter, suggesting that NS3 represses the transcription of p21 by modulating the activity of p53. Although the NS3 protein domain required for the majority of p21 repression was located on the protease domain, the proteinase activity itself does not seem to be necessary for repression. Both transcription and protein stability of p53 were unaffected by NS3, suggesting that NS3 might repress transcription of p21 by inhibiting the regulatory activity of p53 via protein-protein interaction(s). Finally, the growth rate of NS3-expressing cell lines was at least twice as fast as that of the parent NIH 3T3 cells, indicating that the repression of p21 is actually reflected by the stimulation of cell growth.

Original languageEnglish (US)
Pages (from-to)2235-2241
Number of pages7
JournalJournal of General Virology
Volume82
Issue number9
DOIs
StatePublished - Jan 1 2001

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Hepacivirus
Peptide Hydrolases
Binding Sites
NIH 3T3 Cells
Proteins
Protein Stability
Growth
Cell Death
Cell Proliferation
Cell Line
hepatitis C virus NS3 protein
Hepatitis C virus nucleocapsid protein
Protein Domains

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Kwun, Hyun Jin ; Jung, E. Y. ; Ahn, J. Y. ; Lee, M. N. ; Jang, K. L. / P53-dependent transcriptional repression of p21waf1 by hepatitis C virus NS3. In: Journal of General Virology. 2001 ; Vol. 82, No. 9. pp. 2235-2241.
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P53-dependent transcriptional repression of p21waf1 by hepatitis C virus NS3. / Kwun, Hyun Jin; Jung, E. Y.; Ahn, J. Y.; Lee, M. N.; Jang, K. L.

In: Journal of General Virology, Vol. 82, No. 9, 01.01.2001, p. 2235-2241.

Research output: Contribution to journalArticle

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