Document Detail

Identification of E2F1 as an important transcription factor for the regulation of tapasin expression.
MedLine Citation:
PMID:  20663889     Owner:  NLM     Status:  MEDLINE    
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.
Juergen Bukur; Felix Herrmann; Diana Handke; Christian Recktenwald; Barbara Seliger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-27     Completed Date:  2010-10-26     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  30419-26     Citation Subset:  IM    
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle, Saale, Germany.
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MeSH Terms
E2F1 Transcription Factor / genetics,  metabolism*
Gene Expression Regulation / physiology*
Membrane Transport Proteins / biosynthesis*,  genetics
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
Reg. No./Substance:
0/E2F1 Transcription Factor; 0/E2f1 protein, mouse; 0/Membrane Transport Proteins; 0/beta 2-Microglobulin; 0/tapasin; EC Transcription Factors; EC protein, mouse; EC, erbB-2

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