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.