ubiquitinmodifying

Ubiquitin modifying refers to the post-translational modification of proteins through the covalent attachment or removal of ubiquitin and ubiquitin-like modifiers. In ubiquitination, a cascade of enzymes—E1 activating enzyme, E2 conjugating enzyme, and E3 ligase—conjugates ubiquitin to substrates, typically on lysine residues. Polyubiquitin chains can be formed when additional ubiquitin molecules are linked via lysine 48, 63, or other residues, or as linear chains, determining the fate and function of the substrate. K48-linked chains generally signal for proteasomal degradation, while K63- and Met1-linked chains regulate signaling, trafficking, DNA repair, and autophagy. Deubiquitinating enzymes (DUBs) remove ubiquitin, reversing modification and restoring substrate function.

E3 ligases provide substrate specificity and are categorized by catalytic domains, including RING, HECT, and RBR families. DUBs belong to several families such as USP, UCH, OTU, and JAMM. Dysregulation of ubiquitin modifying is implicated in many diseases, including cancer, neurodegeneration, and immune disorders, making components of the system targets for therapeutic intervention. Research methods include mass spectrometry to identify ubiquitination sites, linkage-specific antibodies, and chemical inhibitors of E1, E2, E3 enzymes, or DUBs.

Ubiquitin modifying also encompasses ubiquitin-like modifiers such as NEDD8 and SUMO, which use related enzymatic cascades to alter substrate properties. The field seeks to map modification networks and understand context-dependent outcomes in cells.