Article Figures & Data
Figures
- Figure 1.
Global differential landscape of phosphorylation, ubiquitination, and malonylation modifications in metabolic proteins in CRC. (A) Bar plot showing the number of upregulated and downregulated differential PTM sites for each PTM type in CRC tissues compared to normal tissues. (B) Dot plot showing the dynamic range of log2 FC for phosphorylation, ubiquitination, and malonylation modifications. (C) Average log 2 fold change (log 2FC) for each modification type across all modified proteins, with upregulated modifications shown in positive values and downregulated modifications in negative values. (D) Stacked bar chart depicting the distribution of proteins with different numbers of modification sites for each PTM. (E) Interaction heatmap displaying the overlap of the three PTM types in proteins, with color intensity corresponding to the number of overlapping. Up- and downregulated PTM sites were defined as fold change greater than 1.5 indicating upregulation and fold change less than 1/1.5 indicating downregulation. A p-value <0.05 was considered statistically significant. CRC, Colorectal cancer; PTM, post-translational modification; PPI, protein-protein interaction; KEGG, Kyoto Encyclopedia of Genes and Genomes; BP, biological process; CC, cellular component; MF, molecular function.
- Figure 2.
Intersection features of phosphorylation, ubiquitination, and malonylation in metabolic proteins and their distribution in core metabolic pathways. (A) Venn diagram showing the overlap of phosphorylation (purple), ubiquitination (green), malonylation (orange), and metabolism (blue) related proteins. (B) Log2 FC of phosphorylation, ubiquitination, and malonylation modifications in proteins modified by all three PTM types. Red dots indicate upregulation (log2 FC >0.58), and green dots indicate downregulation (log 2 FC <0.58). (C-F) Distribution of phosphorylation (blue) and ubiquitination (orange) modification sites across key metabolic enzymes: (C) ALDOA, (D) GPI, (E) PKM, and (F) TALDO1. Each plot shows the total number of references for each modification site along the protein sequence, with residue numbers on the x-axis and the total number of references on the y-axis. (G) Bar chart showing the enrichment of Biological Processes (blue), Cellular Components (red), and Molecular Functions (green) for proteins modified by phosphorylation, ubiquitination, and malonylation. The y-axis represents the number of enriched terms, and each bar corresponds to the number of terms associated with the respective PTM type. PTM, Post-translational modification.
- Figure 3.
PTM site localization on 3D structures of key glycolytic enzymes. (A-D) 3D structures of four key glycolytic enzymes, showing the locations of phosphorylation (red), ubiquitination (yellow), and malonylation (purple) modification sites. Each modification site is marked on the protein backbone, with residue numbers indicated. The color coding represents the type of PTMs at each site. (A) ALDOA, (B) GPI, (C) PKM, and (D) TALDO1. PTM, Post-translational modification.
- Figure 4.
GO and KEGG pathway enrichment analysis of PTMs in glycolytic enzymes. (A-C) GO enrichment analysis showing the enrichment of biological process (BP), cellular component (CC), and molecular function (MF) for phosphorylation (A), ubiquitination (B), and malonylation (C). The color gradient from blue to red indicates the p-value significance, with blue representing lower p-values (higher significance) and red representing higher p-values (lower significance). (D-F) KEGG pathway analysis of phosphorylation (D), ubiquitination (E), and malonylation (F). Color intensity indicates the degree of enrichment in each pathway, with darker colors representing higher enrichment. (G) Chord diagram illustrating the relationships between functional pathways and the types of modifications (phosphorylation, ubiquitination, and malonylation). (H-J) Subcellular localization of PTMs: (H) Phosphorylation, (I) Ubiquitination, and (J) Malonylation, with colored regions indicating the distribution of each PTM type in different cellular compartments: Cytoplasm, Nucleus, Mitochondria, and Plasma membrane. PTM, Post-translational modification; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
- Figure 5.
PPI network of multi-modified proteins in metabolic regulation. (A) The functional cluster network showing the interactions between key metabolic enzymes, including glycolytic enzymes, mitochondrial enzymes, and other metabolic regulators. (B) PPI network of key metabolic enzymes, with green nodes representing proteins involved in glycolysis and metabolic regulation, and orange nodes highlighting enzymes with critical modifications such as phosphorylation, ubiquitination, or malonylation. (C) PPI network for enzymes associated with metabolic and cellular functions, with green nodes representing proteins involved in general metabolic regulation and yellow nodes marking proteins like ATIC that are involved in more specific processes. (D) PPI network of proteins associated with ubiquitination, with green nodes indicating stable proteins involved in cellular processes, and orange nodes identifying those with significant modifications that impact stability and interactions. (E) PPI network focusing on enzymes involved in lipid metabolism, with green nodes representing general metabolic regulators and orange nodes highlighting proteins like HMGC2 that are modified by key PTMs and play central roles in metabolic regulation. PPI, Protein-protein interaction.
- Figure 6.
Mechanistic models of metabolic pathway regulation in CRC via PTMs. This diagram illustrates key metabolic enzymes and their PTMs (ubiquitination, phosphorylation, and malonylation) in CRC metabolism. IDH1 mutation produces 2-HG, leading to DNA/histone methylation and epigenetic changes. Ubiquitination of IDH1 enhances its degradation. LDHA is ubiquitinated, promoting lactate production and supporting glycolysis. PDHA1, phosphorylated by PDK1, inhibits the TCA cycle and promotes glycolysis via the Warburg effect. GAPDH undergoes malonylation, modulating glycolytic activity. CRC, Colorectal cancer; PTM, post-translational modification.
- Figure 7.
Schematic diagram of the research workflow and main findings. This figure outlines the comprehensive workflow used in this study, illustrating the integration of multi-omics data acquisition, PTM profiling, and bioinformatic analysis to construct a PTM-driven metabolic regulatory network in CRC. Key steps include the identification of differential PTMs, mapping of modified enzymes, and the construction of a metabolic regulatory network. These findings highlight how PTMs in enzymes like IDH1, LDHA, PDHA1, and GAPDH regulate metabolic pathways, supporting CRC tumor progression and the Warburg effect. CRC, Colorectal cancer; PTM, post-translational modification.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.