Writing, reading, and editing ubiquitin. (A) Ubiquitin is added to a substrate protein (writing ubiquitin) by E3 ligases, and ubiquitin moieties can be removed (editing ubiquitin) by deubiquitylating enzymes (DUBs). Protein degradation is mostly associated with polyubiquitin chains, in which ubiquitin moieties attach to each other via homotypic lysine-48 (K48) linkages or heterotypic K11/K48 linkages (mixed chain or branched; see Ubiquitin signals produced by CRLs and the APC/C text box). The result of K63-linked polyubiquitylation is distinct and, together with monoubiquitylation (monoUb), it is associated with nonproteolytic outcomes. (B) Ubiquitylation produces a signal that is often dependent on effector proteins or complexes (ubiquitin readers). These include the proteasome, which is a proteolytic machine, or the segregase VCP/p97 (Cdc48 in yeast), which extracts proteins from chromatin, cellular compartments, or protein complexes for recycling or degradation. Other ubiquitin-binding proteins can fulfill a specific function with nonproteolytic outcomes when they are recruited to ubiquitylated substrates (e.g., damage tolerance by error-prone polymerases), potentially altering the localization or activity of the ubiquitylated substrate. By affecting protein interactions or conformations, ubiquitylation may directly alter protein localization or activity. A challenge in present research is to distinguish between a passive effect of ubiquitylation and the action of an unidentified ubiquitin reader.