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p53 induces TAP1 and enhances the transport of MHC class I peptides

Oncogene volume 18, pages 7740–7747 (1999)Cite this article

Abstract

The transporter associated with antigen processing (TAP) 1 is required for the major histocompatibility complex (MHC) class I antigen presentation pathway, which plays a key role in host tumor surveillance. Since more than 50% of tumors have a dysfunctional p53, evasion of tumor surveillance by tumor cells may be linked to loss of p53 function. Here we found that TAP1 is strongly induced by p53 and DNA-damaging agents through a p53-responsive element. We also found that p73, which is homologous to p53, is capable of inducing TAP1 and cooperates with p53 to activate TAP1. Furthermore, we found that by inducing TAP1, p53 enhances the transport of MHC class I peptides and expression of surface MHC-peptide complexes, and cooperates with interferon γ to activate the MHC class I pathway. These results suggest that tumor surveillance may be a mechanism by which p53 and/or p73 function as tumor suppressors.

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Acknowledgements

We are grateful to Drs R Markowitz, W Dynan, D Munn, M Iwashima and A Mellor for their critical reading of this manuscript and/or suggestions. We would like to thank H Ploegh (MIT, MA) for human TAP1 cDNA, J Trowsdale (University of Cambridge, UK) for TAP1 genomic DNA, B Seliger (Johannes Gutenberg-Universität, Germany) for anti-TAP1 antibody, D Dransfield (Medical College of Georgia, GA, USA) for HCT116 and LST174T cell lines, B Vogelstein (Johns Hopkins University, MD, USA) for 8OS14 cell line, and A Mellor (Medical College of Georgia, GA, USA) for H2-Kb cDNA. This work is supported in part by grants from the National Institute of Health (CA76069 and CA81237) and DOD Army Breast Cancer Program (DAMD17-97-1-7019).

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  1. Kuichun Zhu, Jian Wang and Jianhui Zhu: K Zhu, J Wang and J Zhu contributed equally to this study

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  1. Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, 30912, Georgia, GA, USA

    Kuichun Zhu, Jian Wang, Jianhui Zhu, Jieyuan Jiang, Jiang Shou & Xinbin Chen

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  1. Kuichun Zhu
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Zhu, K., Wang, J., Zhu, J. et al. p53 induces TAP1 and enhances the transport of MHC class I peptides. Oncogene 18, 7740–7747 (1999). https://doi.org/10.1038/sj.onc.1203235

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