Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP

Asish K. Ghosh, Mainak Majumder, Robert Steele, Peter Yaciuk, John Chrivia, Ranjit Ray, Ratna B. Ray

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Hepatitis C virus NS5A protein transcriptionally modulates cellular genes and promotes cell growth. NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellular transcription factor, SRCAP. The authenticity of this interaction was verified by a mammalian two-hybrid assay, in vitro pull-down experiment, and an in vivo coimmunoprecipitation assay in human hepatoma (HepG2) cells. An in vitro transient transfection assay demonstrated that SRCAP can efficiently activate transcription when recruited by the Ga14 DNA- binding domain to the promoter. However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP. Together these results suggest that the interaction of NS5A and SRCAP may be one of the mechanisms by which NS5A exerts its effect on cell growth regulation contributing to hepatitis C virus-mediated pathogenesis.

Original languageEnglish (US)
Pages (from-to)7184-7188
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number10
DOIs
StatePublished - Mar 10 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ghosh, A. K., Majumder, M., Steele, R., Yaciuk, P., Chrivia, J., Ray, R., & Ray, R. B. (2000). Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP. Journal of Biological Chemistry, 275(10), 7184-7188. https://doi.org/10.1074/jbc.275.10.7184