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J Biol Chem, Vol. 275, Issue 10, 7184-7188, March 10, 2000
From the Departments of 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 Gal4 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.
Hepatitis C Virus NS5A Protein Modulates Transcription
through a Novel Cellular Transcription Factor SRCAP*
,,,
, and**
Pathology,
§ Molecular Microbiology and Immunology, and
¶ Pharmacological and Physiological Sciences, and the
Division of Infectious Diseases and Immunology, Saint Louis
University, St. Louis, Missouri 63104
*
This research was supported by Public Health Service Grants
AI45144 (to R. B. R.) and DK56143 (to R. R.) from the
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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