The family of ubiquitin‐conjugating enzymes (E2s): deciding between life and death of proteins

The FASEB JournalVolume 24, Issue 4 p. 981-993 ReviewFree to Read The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins Sjoerd J. L. van Wijk, Sjoerd J. L. van Wijk Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg, Utrecht, The NetherlandsSearch for more papers by this authorH. T. Marc Timmers, Corresponding Author H. T. Marc Timmers h.t.m.timmers@umcutrecht.nl Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg, Utrecht, The NetherlandsCorrespondence: Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. E-mail: h.t.m.timmers@umcutrecht.nlSearch for more papers by this author Sjoerd J. L. van Wijk, Sjoerd J. L. van Wijk Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg, Utrecht, The NetherlandsSearch for more papers by this authorH. T. Marc Timmers, Corresponding Author H. T. Marc Timmers h.t.m.timmers@umcutrecht.nl Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg, Utrecht, The NetherlandsCorrespondence: Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. E-mail: h.t.m.timmers@umcutrecht.nlSearch for more papers by this author First published: 25 November 2009 https://doi.org/10.1096/fj.09-136259Citations: 27Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat ABSTRACT The family of ubiquitin-conjugating (E2) enzymes is characterized by the presence of a highly conserved ubiquitin-conjugating (UBC) domain. These domains accommodate the ATP-activated ubiquitin (Ub) or ubiquitin-like (UBL) protein via a covalently linked thioester onto its active-site residue. E2 enzymes act via selective protein-protein interactions with the E1 αnd E3 enzymes and connect activation to covalent modification. By doing so, E2s differentiate effects on downstream substrates, either with a single Ub/UBL molecule or as a chain. While E3s are involved in substrate selection, E2s are the main determinants for selection of the lysine to construct ubiquitin chains, which thereby directly control the cellular fate of the substrate. In humans, 35 active E2 enzymes have been identified so far, while other eukaryotic genomes harbor 16 to 35 E2 family members. Some E2s possess Nand/or C-terminal extensions that mediate E2-specific processes. During the past two decades, strong support has led to the control of E2 enzymes in decisions concerning the life or death of a protein. Here, we summarize current knowledge and recent developments on E2 enzymes with respect to structural characteristics and functions. From this we propose a shelllike model to rationalize the selectivity of these key enzymes in directing Ub/UBL-conjugation pathways.— Van Wijk, S. J. L., Timmers, H. T. M. The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins. FASEB J. 24, 981–993 (2010). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2fj09136259-sup-0001.docapplication/doc, 7.3 KB Supplementary Material 1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume24, Issue4April 2010Pages 981-993 RelatedInformation