title: p53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1.
abstract: The p53 tumour suppressor has an important role in cancer cells. Here we show that p53 regulates expression of major histocompatibility complex I on the cell surface. We show that the tumour cell line HCT116, which lacks p53 exhibits significantly lower major histocompatibility complex I expression than its wild-type counterpart. Using a combination of chromatin immunoprecipitation sequencing and gene expression analysis, we demonstrate that p53 upregulates expression of endoplasmic reticulum aminopeptidase 1 by binding to its cognate response element in the ERAP1 gene. Silencing of p53 decreases endoplasmic reticulum aminopeptidase 1 protein levels and therefore major histocompatibility complex I expression. We further show that this mechanism operates in A549 cells infected with H1N1 influenza virus, in which H1N1 activates p53, leading to endoplasmic reticulum aminopeptidase 1 upregulation and a corresponding increase in major histocompatibility complex I expression. Our study suggests a previously unrecognized link between p53 function and the immunosurveillance of cancer and infection.
authors: Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
authors: Bei
authors: B
authors: Wang
authors: Dandan
authors: D
authors: Niu
authors: Liyun
authors: L
authors: Lai
authors: Ee Chee
authors: EC
authors: Ren
mesh_terms: D000626:Aminopeptidases / Q000096:biosynthesis / Q000276:immunology*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism*; D045325:HCT116 Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007157:Immunologic Surveillance / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D015778:Minor Histocompatibility Antigens; D010879:Piperazines / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015395:Histocompatibility Antigens Class I; D007093:Imidazoles; D015778:Minor Histocompatibility Antigens; D010879:Piperazines; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3; D000626:Aminopeptidases; C464841:ERAP1 protein, human
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