1996 Fiscal Year Final Research Report Summary
Regulation of MHC Class I Gene expression by oncogne and anti-oncogene.
| Project/Area Number |
06454604
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | The Institute of Physical and Chemical Research (RIKEN) |
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Principal Investigator |
YOKOYAMA Kazushige Gene Bank, Vice-researcher, ジーンバンク室, 副主任研究員 (80182707)
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| Project Period (FY) |
1994 – 1996
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| Keywords | Adenovirus / MHC class I / EIA / TBP / Negative repression / p300 / MAZ / HMG 1 |
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| Research Abstract |
The primary rodent cells transformed by the oncogenic Ad12 virs expressed reduced amount of class I antigen as opposed to cells transformed by the non-oncogenic Ad5 (2) virs. We study here the mechanism of the transcriptional repression of H-2K^b gene by Ad12-EIA.The promoter assay with the successive 5' end delection and substitution CAT constructs demonstrated the negative regulatory elements were localized in the distal 316 bp sequences (-1835 to 1521). The cell-surface expression of MHC class I cDNA expresssion vector, in which the (CAA) n repeats in the 316 bp region was inserted, as compared with the mutated (CAA) n sequence. The (CAA) n repeats can be contributed to the EIA mediated-negative reperession. These nuclear factors-binding to the negative element has been purified and we isolated the cDNA clones encoded these proteins bound to (CAA) n repeated elements, MAZ (Myc-associated zinc finger protein) and HMG-1. Furthermore, the encoded proteins, which bind to this repeats, were shown to associate with the EIA binding cellular protein, p300 in Ad12-EIA.Second element is the TATA-like sequence located in the far-upstream region. The TBP (or TBP like molecules) can bind to this upstream TATA-like and regular TATA box in a competition binding manner of each site. The p300 cellular protein can also bind this TBP in Ad-EIA.Ths we conclude treat the ELA,MAZ,HMGl and TBP protein complex are directly or indirectly involved in the EIA mediated suppression of MHC class I gene. The EIA protein released the p300 pretein from these complex, to result the negative expression on the MHC class I gene.The protein-protein interaction between these proteins and EIA (condluding p300) was analyzed in vitro and in vivo to study the controlled mechanism of the EIA mediated repression of H-2K^b gene by Ad12-EIA.
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