Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes

Abstract

Ubiquitination involves the attachment of ubiquitin (Ub) to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Polyubiquitination through different lysines (seven) or the N-terminus of Ub can generate different protein-Ub structures. These include monoubiquitinated proteins, polyubiqutinated proteins with homotypic chains through a particular lysine on Ub or mixed polyubiquitin chains generated by polymerization through different Ub lysines. The ability of the ubiquitination pathway to generate different protein-Ub structures provides versatility of this pathway to target proteins to different fates. Protein ubiquitination is catalyzed by Ub-conjugating and Ub-ligase enzymes, with different combinations of these enzymes specifying the type of Ub modification on protein substrates. How Ub-conjugating and Ub-ligase enzymes generate this structural diversity is not clearly understood. In the current review, we discuss mechanisms utilized by the Ub-conjugating and Ub-ligase enzymes to generate structural diversity during protein ubiquitination, with a focus on recent mechanistic insights into protein monoubiquitination and polyubiquitination.

Reciprocal Control of Anaplerotic Phosphoenolpyruvate Carboxylase by in Vivo Monoubiquitination and Phosphorylation in Developing Proteoid Roots of Phosphate-Deficient Harsh Hakea

“…To the best of our knowledge, both discoveries are unprecedented for any metabolic enzyme in nature, including a C 3 PEPC. Monoubiquitination has been more generally implicated in mediating proteinprotein interactions and protein localization to control diverse processes including membrane trafficking, gene expression, and DNA repair and replication (Sadowski et al, 2012). Thus, future studies are needed to assess potential ubiquitin-binding domain proteins that might interact with monoubiquitinated plant PEPCs, as well as the possible influence of this PTM on the enzyme's subcellular localization.…”

Rho GTPases, oxidation, and cell redox control

“…23 These modifications result in the addition of single or multiple ubiquitin moieties (76-residue protein) that affect protein localization, stability, and trafficking. 24 Ras was one of the first GTPases shown to be mono-and diubiquitinated. While ubiquitination of H-Ras promotes endosomal localization, 25,26 monoubiquitination at Lys 147 in K-Ras upregulates K-Ras activity by impairing GAP-mediated GTP hydrolysis.…”

H2B ubiquitination: Conserved molecular mechanism, diverse physiologic functions of the E3 ligase during meiosis

“…Ubiquitin can be removed from target protein by deubiquitin enzymes (DUBs), which are called deubiquitination. [11][12][13] Monoubiquitination of histone H2B at the 123 th Lysine residue in yeast (H2BK123ub) or the 120 th lysine residue in mammals (H2BK120ub) is catalyzed by the E3 ubiquitin ligase Bre1 (RNF20/RNF40 complex in mammals). H2Bub takes part in some of the fundamental biologic processes, including cell cycle, tumogenesis, apoptosis and stem cell differentiation.…”