Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner

N. Majumder, A. K. Ghosh, R. Steele, R. Ray, R. B. Ray

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

We have previously demonstrated that hepatitis C virus (HCV) NS5A protein promotes cell growth and transcriptionally regulates the p21/waf1 promoter, a downstream effector gene of p53. In this study, we investigated the molecular mechanism of NS5A-mediated transcriptional repression of p21/waf1. We observed that transcriptional repression of the p21/waf1 gene by NS5A is p53 dependent by using p53 wild-type (+/+) and null (-/-) cells. Interestingly, p53-mediated transcriptional activation from a synthetic promoter containing multiple p53 binding sites (PG13-LUC) was abrogated following expression of HCV NS5A. Additional studies using pull-down experiments, in vivo coimmunoprecipitation, and mammalian two-hybrid assays demonstrated that NS5A physically associates with p53. Confocal microscopy revealed sequestration of p53 in the perinuclear membrane and colocalization with NS5A in transfected HepG2 and Saos-2 cells. Together these results suggest that an association of NS5A and p53 allows transcriptional modulation of the p21/waf1 gene and may contribute to HCV-mediated pathogenesis.

Original languageEnglish (US)
Pages (from-to)1401-1407
Number of pages7
JournalJournal of Virology
Volume75
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

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Hepatitis C virus
Hepacivirus
Gene Expression
gene expression
promoter regions
Null Lymphocytes
two hybrid system techniques
Two-Hybrid System Techniques
genes
p53 Genes
transcriptional activation
Confocal Microscopy
Transcriptional Activation
Genes
binding sites
cell growth
pathogenesis
Binding Sites
cells
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. / Majumder, N.; Ghosh, A. K.; Steele, R.; Ray, R.; Ray, R. B.

In: Journal of Virology, Vol. 75, No. 3, 2001, p. 1401-1407.

Research output: Contribution to journalArticle

Majumder, N. ; Ghosh, A. K. ; Steele, R. ; Ray, R. ; Ray, R. B. / Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. In: Journal of Virology. 2001 ; Vol. 75, No. 3. pp. 1401-1407.
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