TY - JOUR
T1 - Hepatitis B viral transactivator HBx alleviates p53-mediated repression of α-fetoprotein gene expression
AU - Ogden, Stacey K.
AU - Lee, Kathleen C.
AU - Barton, Michelle Craig
PY - 2000/9/8
Y1 - 2000/9/8
N2 - Chronic infection with hepatitis B virus (HBV) is associated with development of hepatocellular carcinoma (HCC). The exact mechanism by which chronic infection with HBV contributes to onset of HCC is unknown. However, previous studies have implicated the HBV trans-activator protein, HBx, in progression of HCC through its ability to bind the human tumor suppressor protein, p53. In this study, we have examined the ability of HBx to modify p53 regulation of the HCC tumor marker gene, α-fetoprotein (AFP). By utilizing in vitro chromatin assembly of DNA templates prior to transcription analysis, we have demonstrated that HBx functionally disrupts p53-mediated repression of AFP transcription through protein-protein interaction. HBx modification of p53 gene regulation is both tissue-specific and dependent upon the p53 binding element. Our data suggest that the mechanism by which HBx alleviates p53 repression of AFP transcription is through an association with DNA-bound p53, resulting in a loss of p53 interaction with liver-specific transcriptional co-repressors.
AB - Chronic infection with hepatitis B virus (HBV) is associated with development of hepatocellular carcinoma (HCC). The exact mechanism by which chronic infection with HBV contributes to onset of HCC is unknown. However, previous studies have implicated the HBV trans-activator protein, HBx, in progression of HCC through its ability to bind the human tumor suppressor protein, p53. In this study, we have examined the ability of HBx to modify p53 regulation of the HCC tumor marker gene, α-fetoprotein (AFP). By utilizing in vitro chromatin assembly of DNA templates prior to transcription analysis, we have demonstrated that HBx functionally disrupts p53-mediated repression of AFP transcription through protein-protein interaction. HBx modification of p53 gene regulation is both tissue-specific and dependent upon the p53 binding element. Our data suggest that the mechanism by which HBx alleviates p53 repression of AFP transcription is through an association with DNA-bound p53, resulting in a loss of p53 interaction with liver-specific transcriptional co-repressors.
UR - http://www.scopus.com/inward/record.url?scp=0034623236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034623236&partnerID=8YFLogxK
U2 - 10.1074/jbc.M004449200
DO - 10.1074/jbc.M004449200
M3 - Article
C2 - 10842185
AN - SCOPUS:0034623236
SN - 0021-9258
VL - 275
SP - 27806
EP - 27814
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 36
ER -