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(Received for publication, December 4, 1996, and in revised form, March 7, 1997)
From the Division of Infectious Diseases and Immunology, Saint
Louis University, St. Louis, Missouri 63110
Our previous results have suggested that the
putative core protein of hepatitis C virus (HCV) transcriptionally
regulates cellular and viral genes, inhibits cisplatin and
c-myc-mediated apoptotic cell death under certain
conditions, and transforms primary rat embryo fibroblast cells with a
cooperative oncogene. Because HCV appears to cause hepatocellular
carcinoma, we evaluated the regulatory role of the HCV core protein on
p53, a well known tumor suppressor gene, by an in vitro
transfection assay. HCV core protein repressed transcriptional activity
of the p53 promoter when tested separately in COS7 and HeLa cells.
Deletion mutational analysis of the HCV core gene indicated that the
regulatory domain involved in the repression of p53 transcriptional
activity is located around amino acid residues 80-122 encompassing a
putative DNA binding motif and two major phosphorylation sites. Results from this study suggest that the putative core protein may have an
important biological role in the promotion of cell growth by repressing
p53 transcription, and this appears to be consistent with certain
earlier observations about HCV core moving into the nucleus.
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