DIRECT INTERACTION OF THE HEPATITIS-B VIRUS HBX PROTEIN WITH P53 LEADS TO INHIBITION BY HBX OF P53 RESPONSE ELEMENT-DIRECTED TRANSACTIVATION

Citation
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
Citations number
82
Categorie Soggetti
Virology
Journal title
ISSN journal
0022538X
Volume
69
Issue
3
Year of publication
1995
Pages
1851 - 1859
Database
ISI
SICI code
0022-538X(1995)69:3<1851:DIOTHV>2.0.ZU;2-E
Abstract
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,