ubiquitination
Definition
Ubiquitination is a post-translational modification where ubiquitin proteins are covalently attached to target proteins through an enzymatic cascade involving E1 (activating), E2 (conjugating), and E3 (ligase) enzymes. This reversible modification regulates protein degradation via the proteasome, cellular localization, signal transduction, and protein-protein interactions. Ubiquitin can be attached as a single molecule (monoubiquitination) or as polyubiquitin chains with distinct linkage types (K48, K63, etc.), each conferring different cellular fates. Dysregulated ubiquitination is implicated in cancer, neurodegenerative diseases, and immune disorders, making it a critical target for therapeutic intervention and a key focus in proteomics research.
Visualize ubiquitination in Nodes Bio
Researchers can map ubiquitination networks by connecting E3 ligases to their substrate proteins, visualizing how ubiquitin modifications propagate through signaling cascades. Network analysis reveals substrate specificity patterns, identifies regulatory hubs, and traces degradation pathways. Integration with phosphorylation data enables visualization of crosstalk between post-translational modifications, while pathway enrichment analysis highlights disease-relevant ubiquitination circuits affected by genetic perturbations or drug treatments.
Visualization Ideas:
- E3 ligase-substrate interaction networks showing specificity and redundancy patterns
- Ubiquitination cascade networks integrating E1, E2, and E3 enzymes with their target proteins
- Multi-omics networks combining ubiquitination sites with phosphorylation and acetylation modifications
Example Use Case
A cancer research team investigating resistance to proteasome inhibitors uses proteomics to identify differentially ubiquitinated proteins in resistant versus sensitive cell lines. They discover upregulation of specific E3 ligases and altered ubiquitination patterns on oncoproteins. By mapping these changes in a network context, they identify compensatory degradation pathways that bypass proteasome inhibition. This reveals novel E3 ligase targets for combination therapy, with network analysis pinpointing which substrates are most critical for maintaining the resistant phenotype through alternative protein quality control mechanisms.