Fig. 4: MAPK7 (codes for ERK5) promotes nucleotide synthesis and tumor growth by activating PRPS1/2. | Nature Communications

Fig. 4: MAPK7 (codes for ERK5) promotes nucleotide synthesis and tumor growth by activating PRPS1/2.

From: Proteogenomics of diffuse gliomas reveal molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms

Fig. 4

A The scatter plot showing the proteins interacted with ERK5 (two-sided student t test). B Co-immunoprecipitation assay showing that exogenous ERK5 and exogenous PRPS1/2 interact in the U-87MG cells (n = 1). C In vitro assay showing the interaction between ERK5 and PRPS1/2 (n = 1). D Co-immunoprecipitation assay showing that endogenous ERK5 and endogenous PRPS1/2 interact in the human tissues (n = 1). E 5-ethynyl-2′-deoxyuridine (EDU) staining results of ERK5 overexpression and control cells (cells transfected with empty vectors) (n = 5, mean ± SEM, two-sided student t test). F, G Metabolite levels in U-87MG (left) and in U-251MG (right) that received various treatments (n = 5, mean ± SEM, two-sided student t test). H, I The bar plots indicate the comparison of the IMP, AMP and GMP’s concentration (H, n = 3) and EDU staining results (I, n = 4) between PDCs_EGFRAmp&Mut and PDCs_WT (mean ± SEM, two-sided student t test). J EDU staining results of ERK5 knockdown and control cells (cells transfected with scrambled shRNA) (n = 5, mean ± SEM, two-sided student t test). K–M Metabolite levels in cells that received various treatments (K: n = 5; L: n = 5; M: n = 3, mean ± SEM, two-sided student t test). N Proliferation of U-87MG cells associated with various treatments (n = 5, mean ± SEM, two-sided student t test). O Relative PRPS activities of PRPS1/2 isolated from cells after different treatments (n = 3, mean ± SEM, two-sided student t test). P The heatmap indicates the abundance of PRPS1/T225, PRPS2/S41 in the tumor-adjacent and tumor tissues. Heatmap is color-coded based on the expression level, i.e., low (green) and high (red) z-scored abundance (two-sided Wilcoxon test). Q The activity of PRPS1/2 in tumor, tumor-adjacent tissues (n = 12, mean ± SEM, two-sided Wilcoxon test). R The scatter plots indicated the association between the abundance of phosphosites PRPS1/T225, PRPS2/S41 with the expression of cell proliferation markers Ki67 (p value: Spearman-rank correlation). S Survival analysis of PSPR1/T225 (log-rank test, n = 53, Low = 27, High = 26) and PSPR2/S41 (log-rank test, n = 53, Low = 27, High = 26). T The systematic diagram summarizing the impact of the EGFR alterations on promoting tumor cell proliferation through ERK5. Source data are provided as Source Data files.

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