Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue

I Jaitovich-Groisman; N Benlimame; B L Slagle; M H Perez; L Alpert; D J Song; N Fotouhi-Ardakani; J Galipeau; M A Alaoui-Jamali

doi:10.1074/jbc.M010852200

Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue

J Biol Chem. 2001 Apr 27;276(17):14124-32. doi: 10.1074/jbc.M010852200. Epub 2001 Jan 25.

Authors

I Jaitovich-Groisman¹, N Benlimame, B L Slagle, M H Perez, L Alpert, D J Song, N Fotouhi-Ardakani, J Galipeau, M A Alaoui-Jamali

Affiliation

¹ Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, Departments of Medicine, Pharmacology and Therapeutics, Pathology, and Oncology, Faculty of Medicine, McGill University, Montreal H3T 1E2, Canada.

PMID: 11278765
DOI: 10.1074/jbc.M010852200

Abstract

Human hepatitis B virus is a risk factor for the development of hepatocellular carcinoma. The hepatitis B virus x protein (HBx) has been shown to inactivate the p53 tumor suppressor protein and impair DNA repair, cell cycle, and apoptosis mechanisms. Herein we report that HBx represses two components of the transcription-repair factor TFIIH, XPB (p89), and XPD (p80), both in p53-proficient and p53-deficient liver cells. This inhibition is observed while HBx maintains its transactivation function. Expression of HBx in liver cells results in down-regulation of endogenous XPB and XPD mRNAs and proteins; this inhibition is not observed with other TFIIH subunits, XPA or PCNA. In liver tissue from HBx transgenics, XPB and XPD proteins are down-regulated in comparison to matched normal liver tissue. HBx has been shown to interact with Sp1 transcription factor and affects its DNA binding activity. Sp1 is essential for the basal promoter activity of XPB in liver cells and Drosophila SL2 cells. In the Sp1-deficient SL2 cells, HBx-induced XPB and XPD inhibition is Sp1-dependent. In summary, our results provide evidence that HBx represses the expression of key TFIIH proteins at least in part through Sp1 elements; this repression may impair TFIIH function in DNA repair mechanisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Apoptosis
Blotting, Western
Cell Line
Chloramphenicol O-Acetyltransferase / metabolism
DNA Helicases*
DNA Repair / genetics
DNA-Binding Proteins / metabolism*
Down-Regulation
Drosophila
Drosophila Proteins*
Female
Flow Cytometry
Gene Expression Regulation, Viral*
Humans
Immunohistochemistry
Liver / metabolism*
Male
Mice
Mice, Transgenic
Models, Genetic
Plasmids / metabolism
Promoter Regions, Genetic
Proteins / metabolism*
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sp1 Transcription Factor / metabolism
TATA-Binding Protein Associated Factors*
Trans-Activators / genetics*
Trans-Activators / metabolism*
Transcription Factor TFIID*
Transcription Factor TFIIH
Transcription Factors / genetics*
Transcription Factors, TFII*
Transcription, Genetic*
Transcriptional Activation
Transfection
Tumor Cells, Cultured
Viral Regulatory and Accessory Proteins
Xeroderma Pigmentosum Group D Protein

Substances

DNA-Binding Proteins
Drosophila Proteins
Proteins
RNA, Messenger
Sp1 Transcription Factor
TATA-Binding Protein Associated Factors
Taf6 protein, Drosophila
Trans-Activators
Transcription Factor TFIID
Transcription Factors
Transcription Factors, TFII
Viral Regulatory and Accessory Proteins
hepatitis B virus X protein
XPBC-ERCC-3 protein
Transcription Factor TFIIH
Chloramphenicol O-Acetyltransferase
DNA Helicases
Xeroderma Pigmentosum Group D Protein
ERCC2 protein, human
Ercc2 protein, mouse