title: NEDD8 overexpression results in neddylation of ubiquitin substrates by the ubiquitin pathway.
abstract: Ubiquitin and ubiquitin-like proteins use unique E1, E2, and E3 enzymes for conjugation to their substrates. We and others have recently reported that increases in the relative concentration of the ubiquitin-like protein NEDD8 over ubiquitin lead to activation of NEDD8 by the ubiquitin E1 enzyme. We now show that this results in erroneous conjugation of NEDD8 to ubiquitin substrates, such as p53, Caspase 7, and Hif1α, demonstrating that overexpression of NEDD8 is not appropriate for identification of substrates of the NEDD8 pathway.
authors.affiliation: Scottish Institute for Cell Signalling—Protein Ubiquitylation Unit, University of Dundee, Dow Street,Dundee DD1 5EH, UK.
authors.forename: Roland
authors.initials: R
authors.lastname: Hjerpe
authors.forename: Yann
authors.initials: Y
authors.lastname: Thomas
authors.forename: Thimo
authors.initials: T
authors.lastname: Kurz
mesh_terms: D053179:Caspase 7 / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D000075687:NEDD8 Protein; D011743:Pyrimidines / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014452:Ubiquitins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D003517:Cyclopentanes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D011743:Pyrimidines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C471538:UBA1 protein, human; D025801:Ubiquitin; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D053179:Caspase 7; D044764:Ubiquitin-Activating Enzymes; C539933:pevonedistat