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Cloning and functional analyses of the mouse tapasin promoter

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Abstract

The expression of tapasin is critical for an optimized MHC class I assembly and stable MHC class I surface expression. Thus, impaired MHC class I antigen expression of tumors can be attributable to tapasin downregulation. In order to understand the molecular mechanisms of deficient tapasin expression, the mouse tapasin promoter region and its 5′-flanking sequences were characterized. The mouse tapasin promoter lacks the TATA box and its transcription is initiated at multiple sites within a 51-nucleotide stretch. Sequence analyses revealed transcription factor binding motifs for NF-κB, GATA, E2F, p300, AP1, SP1 and IRF-1/2. Detailed analysis of deletion mutants and elimination of transcription factor binding motifs demonstrated an important role of NF-κB at position −468 for its basal activity, whereas E2F at position −229 represses constitutive promoter activity. Furthermore, the IRF-1/2 binding site is required for gamma interferon inducibility of the tapasin promoter in vitro, but also negatively interferes with its constitutive activity. Thus, characterization of the tapasin promoter represents the molecular basis for the understanding of the heterogeneous expression levels of tapasin under physiological and pathophysiological conditions.

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Acknowledgements

We would like to thank Ursula Wollscheid for excellent technical assistance and I. Schmidt and J. Lösow for significant secretarial assistance. This work is part of the PhD thesis of Felix Herrmann. This work was supported by the MAIFOR program of the Johannes Gutenberg University and the Deutsche Forschungsgemeinschaft SFB 432, project A5.

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Authors and Affiliations

  1. III. Department of Internal Medicine, Johannes Gutenberg University, 55131, Mainz, Germany

    Felix Herrmann, Christoph Huber & Barbara Seliger

  2. Department of Pathology and Cambridge Institute of Medical Research, Cambridge, UK

    John Trowsdale

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  1. Felix Herrmann
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  4. Barbara Seliger
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Correspondence to Barbara Seliger.

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Herrmann, F., Trowsdale, J., Huber, C. et al. Cloning and functional analyses of the mouse tapasin promoter. Immunogenetics 55, 379–388 (2003). https://doi.org/10.1007/s00251-003-0597-2

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  • DOI: https://doi.org/10.1007/s00251-003-0597-2

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