1994 Fiscal Year Final Research Report Summary
The mechanism of Epstein-Barr Virus Promotor-specific transactivation by Z protein
| Project/Area Number |
05670277
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SATO Hiroshi Kanazawa University, Cancer Research Institute Research, Associate, がん研究所, 助手 (00115239)
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| Project Period (FY) |
1993 – 1994
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| Keywords | EB virus / BZLF 1 / Z protein / AP-1 / Fus / BMRF 1 / BHRF 1 / Transcription factor |
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| Research Abstract |
Epstein-Barr virus (EBV) immediate early gene BZFL1 encodes a transcription factor Z protein which induces EBV lytic cycle in latently infected cells. The Z protein shows an amino acid sequence homology with the members of cellular AP-1 family transcription factors, especially Fos proteins. Both Z proteins and AP-1 family members recognize and bind to the same DNA sequence, but Z cannot activate transcription from promotors of cellular genes which are stimulated by cellular AP-1 family members. In an attempt to analyze the mechanism of EBV promotor-specific transactivation by Z,chimeric proteins of Z and Fos were constructed and examined for their transactivation ability using EBV BMRF1, BHRF1, cellular 92-kDa type IV collagenase and Timp gene promotors as reporters. The region from amino acid 100 to 110 of Z,especially 4 gulutamine residues Gln 102,104,105 and 108 in this region, is essential for activation of viral promotors. Furthermore, Z proteins which had amino acid substitution of Gln 108 activated the transcription from 92-kDa type IV collagenase and Timp promotors which cannot be stimulated by the wild type Z.The promotor specificity of Z was also altered by substitution of the region from amino acid 162 to 169 adjacent to DNA binding domains with the corresponding region of Fos proteins. Formations of heterodimers of the wild type Z and chimeric proteins of deletion mutants affected transactivation ability and promotor specificity of them. These results suggest that the structure of dimer forms of Z proteins decides the transacitivation ability and promotor specificity.
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