Positive Transcription Elongation Factor b (P-TEFb) Participates in the HCV Core Protein-induced p53 Transcriptional Activity

• Main Authors: Cheng-Feng Wang, 汪政鋒
• Other Authors: Yueh-Hsin Ping
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/22135621587689462961

碩士 === 國立陽明大學 === 藥理學研究所 === 94 === The interactions between HCV core protein and p53 play an important role in the HCV-associated pathogenesis, including hepatitis and hepatocellular carcinoma. HCV core protein could interact with p53 directly. Recently, there was a report which suggested that HCV core protein enhanced the transcriptional activity of p53. There was a possibility that positive transcription factors may be involved in the HCV core protein-induced p53 transcriptional activity. Positive transcription elongation factor b (P-TEFb), one of the positive transcription factors, can stimulate transcription elongation by RNA Polymerase II to increase gene transcription. It was reported that P-TEFb could phosphorylate p53. In addition, HCV core protein mediated repression of the basal transcriptional activity of HIV-1 LTR was abrogated by the Tat protein. HCV core protein may compete with HIV Tat protein to associate with P-TEFb and repress the HIV-1 LTR promoter activity. Hence, P-TEFb may participate in the HCV core protein-induced p53 transcriptional activity. Using p53-luciferase reporter assay, it was found that HA-HCV core protein-induced p53 activity was inhibited when DRB, a pharmacological P-TEFb inhibitor, was applied. The result of co-immunoprecipitation showed that p53 associated with P-TEFb in the presence of HCV core protein. The complex was recruited to the promoter region of p21 gene directly. Because P-TEFb binds to the promoter region of p21 DNA, there was an increased transcriptional activity of p21 gene. Taken together, the HCV core protein could enhance p53 transcriptional activity by stimulating p53 to interact with P-TEFb. This may provide a novel direction toward the development of drugs against the HCV-associated pathogenesis and cancer.