Open AccessDeubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases
Author(s) -
Virginia De Cesare,
Daniel Carbajo López,
Peter D. Mabbitt,
Adam J. Fletcher,
Mathieu Soetens,
Odetta Antico,
Nicola T. Wood,
Satpal Virdee
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2006947118
Subject(s) - deubiquitinating enzyme , ubiquitin , lysine , biochemistry , threonine , ubiquitins , biology , catalytic triad , enzyme , chemistry , amino acid , ubiquitin ligase , active site , serine , gene
Significance Ubiquitination involves the covalent attachment of the protein ubiquitin to substrates. It can be reversed by the action of deubiquitinating enzymes (DUBs), thereby providing an important layer of regulation. Originally believed to be restricted to lysine residues, it is emerging that additional amino acids, including serine, threonine and cysteine, are also modified. It remains unknown which DUBs might target these unusual sites for deubiquitination. Herein, we develop representative model substrates and screen 53 DUBs for non-lysine activity, thereby providing important insights into DUB function. Strikingly, we find that a poorly studied DUB class has potent and highly selective serine/threonine activity. These findings suggest that non-lysine ubiquitination rivals the regulatory sophistication of its conventional counterpart and might serve distinct cellular functions.