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.

Background: Chemoresistance prevents effective therapy of hepatocellular carcinoma (HCC). Results: Genomic and mechanistic studies suggested the role of miR-193a-3p via SRSF2 mediates up-regulation of the proapoptotic splicing form of caspase 2 in HCC 5-FU resistance. Conclusion:We identify a novel molecular mechanism underlying 5-FU resistance in HCC. Significance: These molecular events identified provide a set of prognostic markers for future rational 5-FU therapy in HCC.

In order to rationally manipulate the cellular metabolism of Escherichia coli for D: -lactate production, single-gene and multiple-gene deletions with mutations in acetate kinase (ackA), phosphotransacetylase (pta), phosphoenolpyruvate synthase (pps), pyruvate formate lyase (pflB), FAD-binding D-lactate dehydrogenase (dld), pyruvate oxidase (poxB), alcohol dehydrogenase (adhE), and fumarate reductase (frdA) were tested for their effects in two-phase fermentations (aerobic growth and oxygen-limited production). Lactate yield and productivity could be improved by single-gene deletions of ackA, pta, pflB, dld, poxB, and frdA in the wild type E. coli strain but were unfavorably affected by deletions of pps and adhE. However, fermentation experiments with multiple-gene mutant strains showed that deletion of pps in addition to ackA-pta deletions had no effect on lactate production, whereas the additional deletion of adhE in E. coli B0013-050 (ackA-pta pps pflB dld poxB) increased lactate yield. Deletion of all eight genes in E. coli B0013 to produce B0013-070 (ackA-pta pps pflB dld poxB adhE frdA) increased lactate yield and productivity by twofold and reduced yields of acetate, succinate, formate, and ethanol by 95, 89, 100, and 93%, respectively. When tested in a bioreactor, E. coli B0013-070 produced 125 g/l D-lactate with an increased oxygen-limited lactate productivity of 0.61 g/g h (2.1-fold greater than E. coli B0013). These kinetic properties of D-lactate production are among the highest reported and the results have revealed which genetic manipulations improved D-lactate production by E. coli.