X protein of hepatitis B virus functions as a transcriptional corepressor on the human telomerase promoter.
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.
Su
Jiun-Ming
JM
Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Lai
Xiang-Me
XM
Lan
Keng-Hsin
KH
Li
Chung-Pin
CP
Chao
Yee
Y
Yen
Sang-Hue
SH
Chang
Full-Young
FY
Lee
Shou-Dong
SD
Lee
Wei-Ping
WP
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
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