R. Truant et al., DIRECT INTERACTION OF THE HEPATITIS-B VIRUS HBX PROTEIN WITH P53 LEADS TO INHIBITION BY HBX OF P53 RESPONSE ELEMENT-DIRECTED TRANSACTIVATION, Journal of virology, 69(3), 1995, pp. 1851-1859
Hepatitis B virus is a major risk factor in human hepatocellular carci
nomas, We have used protein affinity chromatography to show that the 1
7-kDa hepatitis B virus gene product, HBx, binds directly to the human
tumor suppressor gene product, p53. Interaction of HBx with p53 did n
ot prevent p53 from specifically binding DNA, Instead, HBx enhanced p5
3's oligomerization state on a DNA oligonucleotide containing a p53 re
sponse element. Optimal binding of HBx to p53 required intact p53, but
weaker binding to both the N-terminal activation domain of p53 and a
protein fragment containing the C-terminal DNA-binding and oligomeriza
tion domains of p53 was observed. In transient transfection experiment
s with human Calu-6 cells, HBx inhibited transactivation by p53 of a r
eporter gene containing a p53 response element. Also, HBx inhibited p5
3-stimulated transcription in vitro even when added to the reaction mi
xture after the formation of the preinitiation complex Interaction of
HBx with p53 did not prevent the activation domain of p53 from binding
two general initiation factors, the TATA-box binding protein subunit
of TFIID and the p62 subunit of TFIIH. To explain these results, we pr
opose that localization of HBx to a promoter by interaction with DNA-b
ound p53 enables a repression domain in HBx to directly contact the ba
sal transcription machinery and thereby repress transcription,