Figure 1.

The misregulated expression of E2 ubiquitin conjugating enzymes and E3 ubiquitin ligases in various human cancers. The ubiquitination reaction initiates with the activation of ubiquitin by ATP, in which ubiquitin is then transferred to the active site of E1 ubiquitin conjugating enzyme. The E1 transfers the ubiquitin to a Cys in the catalytic active site of the E2 ubiquitin conjugating enzyme. The HECT domain E3 ligases ubiquitinate the target substrates by 2 mechanisms: first, the ubiquitin is transferred from the active site of the E2 to the Cys in the active site of the E3, which then ubiquitinates the Lys residue in the target substrate. RING- and RING-related domain E3 ligases, in contrast, serve as scaffolds to ubiquitinate target substrates in one step: the E2 transfers the ubiquitin directly to the Lys residue in the target substrate. Various tumors take advantage of the misregulated expression of E2s and E3s for the aberrant activation of oncogenic pathways. E2s and E3s colored in green indicate the importance of their expression or overexpression in cancer, while those in red indicate their downregulated expression in cancer. These genomic events result in cancer cell proliferation, migration, invasion, angiogenesis, hypoxia, EMT and metastasis.