Fig. 6: iASPP Deficiency Increases Cell-Autonomous Expression of Tolerogenic Mediators and DAMPs.
From: Regulation of immunological tolerance by the p53-inhibitor iASPP
A Flow cytometry histograms (left) and quantification (right) of PD-L1 and PD-1H expression by transformed KC (blue) or KC;iASPPΔ8/Δ8 (red) pancreatic tumor cells. MFI, median fluorescent intensity. B Differentially regulated genes in A549 cells following iASPP (PPP1R13L) knockdown. A gene is considered as differentially regulated when the mNET-seq and two ChIP-seq pol II signals in the gene body (TSS + 500 bp to poly(A) site) were >2-fold increased (upregulated, blue) or decreased (downregulated, red) in the knockdown cell line versus wild type cell line. The number of differentially expressed genes is indicated for each category. The genes indicated on the left and right sides are the 15 most downregulated or upregulated genes. C Ranked analysis of transcription factor binding sites in down (blue) or up (red)-regulated genes from the total pol II mNET-seq analysis in A549 cells following iASPP (PPP1R13L) knockdown. Transcription factor enrichment in up or down regulated genes was calculated using DAVID. D Motif analysis of indicated transcription factor binding sites in A549 cells following iASPP (PPP1R13L) knockdown. E Heatmap of log2FC in gene expression of indicated immune-related genes following iASPP (PPP1R13L) knockdown in A549 cells quantified by total pol II mNET-seq. The presence of a TP53 ChIP peak or TP53, AP-1, or NFκB 1/2 binding motif is indicated to the right for each gene. AP-1 and NFκB -1 motif presence was determined by GSEA and p53 motif presence was determined by MEME. F Network plot of gene ontology analysis of differentially expressed genes following iASPP (PPP1R13L) knockdown in A549 cells measured by total pol II mNET-seq. Tan circles represent gene sets and colored dots represent genes colored by log2FC.
