- 作者: Chih-Fei Kao; Shiow-Yi Chen; Yan-Hwa Wu Lee
- 作者服務機構: Institute of Biochemistry, National Yang-Ming University, Taipaei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: The hepatitis C virus(HCV) core protein has been impli-cated in the transregulation of various RNA polymerase(Pol)II dependent genes as well as in the control of cellu-lar growth and proliferation. In this study, we show thatthe core protein,whether individually expressed or pro-duced as part of the HCV viral polyprotein,is the onlyviral product that has the potential to activate RNA Pol ltranscription. Deletion analysis demonstrated that thefragment containing the N-terminal 1一156 residues, butnot the 1-122 residues, of HCV core protein confers thesame level of transactivation activity as the full-lengthprotein·Moreover, the integrity of the Ser"116 and Arg'117residues of HCV core protein was found to be critical forits transregulatory functions.We used DNA affinity chro-matography to analyze the human ribosomal RNA pro-moter associated transcription machinery, and the re-suits indicated that recruitment of the upstream bindingfactor and RNA Pol l to the ribosomal RNA promoter isenhanced in the presence of HCV core protein.Addition-ally, the HCV core protein mediated activation of ribo-somal RNA transcription is accompanied by the hyper-phosphorylation of upstream binding factor on serineresidues, but not on threonine residues.Moreover, HCVcore protein is present within the RNA Pol l multiproteincomplex, indicating its direct involvement in facilitatingthe formation of a functional transcription complex. Pro-tein-protein interaction studies further indicated thatHCV core protein can associate with the selectivity factor(SL1)via direct contact with a specific component, TATA-binding protein (TBP).Additionally,the HCV core proteinin cooperation with TBP is able to activate RNA Pol II andPot III mediated transcription,in addition to RNA Pot ltranscription.Thus, the results of this study suggest thatHCV has evolved a mechanism to deregulate all threenuclear transcription systems, partly through targetingof the common transcription factor, TBP. Notably, theability of the HCV core protein to upregulate RNA Pol land Pol III transcription supports its active role in pro-moting cell growth,proliferation,and the progression ofliver carcinogenesis during HCV infection.
- 中文關鍵字: --
- 英文關鍵字: --