title: X protein of hepatitis B virus functions as a transcriptional corepressor on the human telomerase promoter.
abstract: The X protein of hepatitis B virus (HBx) is essential for transactivation of hepatitis B viral and host cellular genes. It has been specifically implicated in the development of hepatocellular carcinoma; however, the molecular mechanism remains unknown. Telomeres, the DNA-protein complexes at the ends of eukaryotic chromosomes, protect chromosomes from degradation at the terminal regions, fusion with a broken DNA end, and inappropriate recombination. The shortening of telomeres that occurs during hepatocellular carcinogenesis has been well studied. In the present study, we isolated an HBx isoform that resulted in telomere shortening in hepatoma cell lines. We found that this HBx isoform down-regulated the expression of human telomerase by transcriptionally repressing its promoter. To further determine the molecular mechanism, we examined human telomerase promoter and identified myc-associated zinc finger protein (MAZ) as a transcriptional repressor of the promoter. We found that the HBx isoform achieved transcriptional suppression of human telomerase by enhancing MAZ binding to its consensus sequence in the promoter through physical association with MAZ.
  
  
  CONCLUSIONS
  The data suggest that HBx can induce telomere shortening by acting as a transcriptional corepressor of MAZ on the human telomerase promoter.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jiun-Ming
authors.initials: JM
authors.lastname: Su
authors.forename: Xiang-Me
authors.initials: XM
authors.lastname: Lai
authors.forename: Keng-Hsin
authors.initials: KH
authors.lastname: Lan
authors.forename: Chung-Pin
authors.initials: CP
authors.lastname: Li
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.forename: Sang-Hue
authors.initials: SH
authors.lastname: Yen
authors.forename: Full-Young
authors.initials: FY
authors.lastname: Chang
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology; D016259:Genes, myc; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D012097:Repressor Proteins / Q000502:physiology*; D019098:Telomerase / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C076035:c-MYC-associated zinc finger protein; C057628:hepatitis B virus X protein; D019098:Telomerase