p53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1

• Published in: Nature communications Vol. 4; no. 1; p. 2359
• Main Authors: Wang, Bei, Niu, Dandan, Lai, Liyun, Ren, Ee Chee
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 22.08.2013; Nature Pub. Group
• Subjects: Aminopeptidases - biosynthesis; Aminopeptidases - immunology; Cell Line, Tumor; Chromatin Immunoprecipitation; Endoplasmic Reticulum - immunology; Endoplasmic Reticulum - metabolism; HCT116 Cells; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - immunology; Humans; Imidazoles - metabolism; Immunologic Surveillance - immunology; Influenza A Virus, H1N1 Subtype - immunology; Minor Histocompatibility Antigens; Piperazines - metabolism; RNA Interference; RNA, Small Interfering; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Up-Regulation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3359

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.