Hepatitis delta antigen regulates the expression of transcription factor TAp63

Autor: Pei-Yin Shih, 施佩吟
Rok vydání: 2008
Druh dokumentu: 學位論文 ; thesis
Popis: 96
Hepatitis delta virus (HDV) is a spherical enveloped virus. The viral genome consists of a single-stranded, negative sense, circular RNA of 1.7 kb that encodes the only known HDV protein, hepatitis delta antigen (HDAg). There are two forms of delta antigen, a small delta antigen (HDAg-S, 195 amino acids, 24 kDa) and a large delta antigen (HDAg-L, 214 amino acids, 27 kDa). HDAg-S is essential for the viral genome replication, whereas HDAg-L is required for the viral assembly. HDV is a satellite virus that requires hepatitis B virus as its helper virus to provide surface antigen (HBsAg) for natural transmission. Although it is known that HDV infection increases liver disease severity, the underlying mechanisms are poorly understood. Previous studies have demonstrated that HDAg-L could activate serum response factor-associated transcription and TGF-β signaling pathway. To further understand the role of HDAg in the expression of host genes, chromatin immunoprecipitation assay was conducted in this study. The results emonstrated that both HDAg-L and HDAg-S bound to the promoter region of plasminogen activator inhibitor (PAI-1) gene. In addition, immunoprecipitation followed by LC-MS/MS analysis were performed to identify other cellular factors that interact with HDAg. Results showed that p63, a member of p53 family, known to be involved in the transcription regulation of cell growth and differentiation was identified to be associated with HDAg. Further studies demonstrated that TAp63γ, an isoform of p63, interacted with both HDAg-L and HDAg-S. Moreover, the expression levels of TAp63γ mRNA and protein were remarkedly increased in cells stably expressing HDAg-L. How HDAg regulates expression of host genes through p63 remains to be elucidated.
Databáze: Networked Digital Library of Theses & Dissertations
Externí odkaz: