FIGURE 2 from A Novel Class of Ribosome Modulating Agents Exploits Cancer Ribosome Heterogeneity to Selectively Target the CMS2 Subtype of Colorectal Cancer

Abstract

<p>ZKN-157 selectively inhibits new protein synthesis in a sensitive colorectal cancer cell line. <b>A,</b> Volcano plot showing heavy-isotope intensities (newly synthesized protein abundance) for 2867 proteins detected at 24-hour timepoint. Protein were classified as follows: Decreased (log<sub>2</sub>FC < −0.4, <i>P</i><sub>adjusted</sub> < 0.05, red), Downward Trend (log<sub>2</sub>FC < −0.4, <i>P</i><sub>adjusted</sub> > 0.05, pink), Increased (log<sub>2</sub>FC > 0.4, <i>P</i><sub>adjusted</sub> < 0.05, dark green), Upward Trend (log<sub>2</sub>FC > 0.4, <i>P</i><sub>adjusted</sub> > 0.05, light green), Unchanged (−0.4 < log<sub>2</sub>FC < 0.4, <i>P</i><sub>adjusted</sub> > 0.05, dark gray). Dotted lines indicate −0.5 and 0.5 log<sub>2</sub>FC values. <b>B,</b> Bar graph plotting percent protein fraction of heavy-isotope intensity (categorized as in <b>A</b>) at 24-hour timepoint versus positively charged regions. Positive charge windows were generated by assigning K and R residues a positive 1 charge and all other amino acid residues a charge of 0. Average charge values were then calculated along a 10-amino acid long sliding window for each protein's amino acid sequence (starting at the first residue and ending at the last complete set of 10 residues). <b>C,</b> Overrepresentation analysis and pathway enrichment in significantly downregulated proteins from <b>A</b> are shown. Count refers to the number of genes found in each pathway while gene ratio refers to the count divided by all genes in the pathway. <b>D,</b> Bar graph showing nascent protein abundance for 68 Ribosomal proteins from heavy-isotope intensity analysis at 24-hour timepoint (categorized as in <b>A</b>). The dotted line indicates −0.4 log<sub>2</sub>FC value.</p>