Your browser does not support JavaScript!



劉世東(Shih-Tung Liu




學校/國家Univ. of California, Berkeley/USA




研究室現有: 博士後研究員2






A comprehensive library of mutations of Epstein-Barr virus

A mutant library of 249 mutants with mutations that span the entire Epstein–Barr virus (EBV) genome was generated by transposition with EZ : : TN ,KAN-2. and insertion with an apramycin resistance gene by a PCR-targeting method. This study also demonstrates the feasibility of generating deletions and site-specific mutations in the BRLF1 promoter on the EBV genome to determine the regions in the promoter that are crucial to transcription. Analysing BZLF1 and BRLF1 mutants by microarray analysis revealed that these two genes regulate the transcription of EBV lytic genes differently. A BZLF1 mutation affects global expression of EBV lytic genes; almost no lytic gene is expressed by the mutant after lytic induction. However, although a BRLF1 mutant still transcribes most lytic genes, the expression of these lytic genes is inefficient. Furthermore, this study shows that the proximal Zta-response element in the BRLF1 promoter is crucial to BRLF1 transcription from the EBV genome, despite the fact that another work demonstrated that this site was unimportant in transient transfection analysis. Furthermore, mutants with a mutation in BDLF1 and BORF1 cannot assemble viral capsids. Results of this study demonstrate the usefulness of a comprehensive mutant library in genetic analyses of EBV.

Nonribosomal Synthesis of Fengycin on an Enzyme Complex Formed by Fengycin Synthetases

Fengycin, a lipopeptidic antibiotic, is synthesized nonribosomally by five fengycin synthetases (FenC, FenD, FenE, FenA, and FenB) in Bacillus subtilis F29-3. This work demonstrates that these fengycin synthetases interlock to form a chain, which coils into a 14.5-nm structure. In this chain, fengycin synthetases are linked in the order FenC-FenDFenE- FenA-FenB by interactions between the C-terminal region of an upstream enzyme and the N-terminal region of its downstream partner enzyme, with their amino acid activation modules arranged collinearly with the amino acids in fengycin. This work also reveals that fengycin is synthesized on this fengycin synthetase chain, explaining how fengycin is synthesized efficiently and accurately. The results from this investigation demonstrate that forming a peptide synthetase complex is crucial to nonribosomal peptide synthesis.

Sumoylation of Rta of Epstein-Barr virus is preferentially enhanced by PIASxβ

Histone acetylation alters the chromatin structure and activates the genes that are repressed by histone deacetylation. This investigation demonstrates that treating P3HR1 cells with trichostatin A (TSA) activates the Epstein-Barr virus (EBV) lytic cycle, allowing the virus to synthesize three viral lytic proteins-Rta, Zta and EA-D. Experimental results indicate that TSA and 12-O:-tetradecanoylphorbol-13-acetate synergistically activate the transcription of BRLF1, an immediate-early gene of EBV. Chromatin immunoprecipitation assay reveals that histone H4 at the BRLF1 promoter is acetylated after P3HR1 cells are treated with TSA, suggesting that histone acetylation activates BRLF1 transcription. Furthermore, results in this study demonstrate that mutation of a YY1-binding site in the BRLF1 promoter activates BRLF1 transcription 1.6- and 2.3-fold in P3HR1 cells and C33A cells, respectively. Real time PCR analysis reveals that the mutation also increases the histone acetylation level of the nucleosomes at the BRLF1 promoter 1. 64- and 3.08-fold in P3HR1 and C33A cells, respectively. Results presented herein suggest that histone deacetylation plays an important role in maintaining the viral latency and histone acetylation at the BRLF1 promoter allows the virus to express Rta and to activate the viral lytic cycle.



1.          C.-Y. Wu, C.-L. Chen, Y.-H. Lee, Y.-C. Cheng, Y.-C. Wu, H.-Y. Shu, F. Götz, and S.-T. Liu. 2007. Nonribosomal Synthesis of Fengycin on an Enzyme Complex Formed by FengycinSynthetases. J. Biol. Chem.282:5608-5616.

2.          Y.-F. Chiu, C.-P. Tung, Y.-H. Lee, W.-H. Wang, C. Li, J.-Y. Hung, C.-Y. Wang, and S.-T. Liu. 2007. A Comprehensive Library of Mutations of Epstein-Barr Virus. J. Gen. Virol.88:2463-2472.

3.          M.-H. Lin, and S.-T. Liu. 2008. Stabilization of pSW100 from Pantoeastewartii by F conjugation system. J. Bacteriol.190:3681-3689.

4.          L.-K. Chang, S.-T. Liu, C.-W. Kuo, W.-H. Wang, J.-Y. Chuang, E. Bianchi, and Y.-R. Hong. 2008. Enhancement of Transactivation Activity of Rta of Epstein-Barr Virus by RanBPM. J. Mol. Biol. 379:231-242.

5.          Y.-H. Lee, Y.-F. Chiu, W.-H. Wang, L.-K. Chang, and S.-T. Liu. 2008. Activation of the ERK signal transduction pathway by Epstein-Barr virus immediate-early protein Rta. J. Gen. Virol.89(10):2437-2446.

6.          W.-J. Ke, B.-Y. Chang, T.-P. Lin, and S.-T. Liu. 2009. Activation of the Promoter of the FengycinSynthetase Operon by the UP Element. J. Bacteriol. 191(14):4615-4623.

7.          C.-Y. Yen, M.-C. Lu, C.-C. Tzeng, J.-Y. Huang, H.-W. Chang, R.-S. Chen, S.-Y. Liu, S.-T. Liu, B. Shieh, and C. Li. 2009. Detection of EBV Infection and Gene Expression in Oral Cancer from Patients in Taiwan by Microarray Analysis. J. Biomed Biotechnol. Volume 2009, Article ID 904589, 15 pages, doi:10.1155/2009/904589.

8.          L.-K. Chang, J.-Y. Chuang, MitsuyoshiNakao, and S.-T. Liu. 2010. MCAF1 and synergistic activation of the transcription of Epstein-Barr virus lytic genes by Rta and Zta. Nucleic Acids Res. 38(14):4687-4700.doi:10.1093/nar/gkq243.

9.          Y.-C. Wu, and S.-T. Liu. 2010. A Sequence That Affects the Copy Number and Stability of pSW200 and ColE1. J. Bacteriol. 192(14):3654-3660.

10.      W.-H. Wang, L.-K. Chang, and S.-T. Liu. 2011. Molecular interactions of Epstein-Barr virus capsid proteins. J. Virol.85(4):1615-1624.

11.      M.-H. Lin, F.-R. Chang, M.-Y. Hua, Y.-C. Wu, and S.-T. Liu. 2011. Inhibitory effects of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose on biofilm formation by Staphylococcus aureus. Antimicrob. Agents Ch.55(3):1021-1027.

12.      C.-W. Kuo, W.-H. Wang, and S.-T. Liu. 2011. Mapping Signals that Are Important for Nuclear and Nucleolar Localiztion in MCRS2. Mol. Cells31(6):547-552.

13.      C.-P. Tung, F.-R. Chang, Y.-C. Wu, D.-W. Chuang, A. Hunyadi, and S.-T. Liu. 2011. Inhibition of the Epstein-Barr virus lytic cycle by protoapigenone. J. Gen. Virol.92(8):1760-1768.

14.      Y.-F. Chiu, B. Sugden, P.-J. Chang, L.-W. Chen, Y.-J. Lin, Y.-C. Lan, C.-H. Lai, J.-Y. Liou, S.-T. Liu, and C.-H. Hung. 2012. Characterization and Intracellular Trafficking of Epstein-Barr Virus BBLF1, a Protein Involved in Virion Maturation. J. Virol.86(18):9647-9655.


  • 友善列印
  • 新增到收藏夾
  • 分享
Voice Play