| Identification of E2F1 as an important transcription factor for the regulation of tapasin expression. | |
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MedLine Citation:
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PMID: 20663889 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HER-2/neu overexpression in tumor cells caused abnormalities of MHC class I surface expression due to impaired expression of components of the antigen-processing machinery (APM) including the low molecular weight proteins, the transporter associated with antigen processing (TAP), and the chaperone tapasin, whereas the expression of MHC class I heavy chain as well as β(2)-microglobulin was only marginally affected. This oncogene-mediated deficient APM component expression could be reverted by interferon-γ treatment, suggesting a deregulation rather than structural alterations as underlying molecular mechanisms. To determine the level of regulation, the transcriptional activity of APM components was analyzed in HER-2/neu(-) and HER-2/neu(+) cells. All major APM components were transcriptionally down-regulated in HER-2/neu(+) when compared with HER-2/neu(-) cells, which was accompanied by a reduced binding of RNA polymerase II to the APM promoters. Site-directed mutagenesis of the p300- and E2F-binding sites in the APM promoters did not reconstitute the oncogene-mediated decreased transcription rate with the exception of tapasin, which was restored in HER-2/neu(+) cells to levels of wild type tapasin promoter activity in HER-2/neu(-) fibroblasts. The E2F-directed control of tapasin expression was further confirmed by chromatin immunoprecipitation analyses showing that E2F1 and p300 bind to the tapasin and APM promoters in both cell lines. Moreover, siRNA-mediated silencing of E2F1 was associated with an increased tapasin expression, whereas transient overexpression of E2F1 launch a reduced tapasin transcription, suggesting that E2F1 is an essential transcription factor for tapasin. |
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Authors:
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Juergen Bukur; Felix Herrmann; Diana Handke; Christian Recktenwald; Barbara Seliger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-27 Completed Date: 2010-10-26 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 30419-26 Citation Subset: IM |
Affiliation:
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Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle, Saale, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals E2F1 Transcription Factor / genetics, metabolism* Gene Expression Regulation / physiology* Membrane Transport Proteins / biosynthesis*, genetics Mice Mutagenesis, Site-Directed NIH 3T3 Cells Receptor, erbB-2 / genetics, metabolism Response Elements / physiology* beta 2-Microglobulin / genetics, metabolism p300-CBP Transcription Factors / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/E2F1 Transcription Factor; 0/E2f1 protein, mouse; 0/Membrane Transport Proteins; 0/beta 2-Microglobulin; 0/tapasin; EC 2.3.1.48/p300-CBP Transcription Factors; EC 2.7.10.1/Erbb2 protein, mouse; EC 2.7.10.1/Receptor, erbB-2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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