title: Characterization of the mammalian family of DCN-type NEDD8 E3 ligases.
abstract: Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit. DCNs are NEDD8 E3 ligases that promote neddylation. Mammalian cells express five DCN-like (DCNL) proteins but little is known about their specific functions or interaction partners. We found that DCNLs form stable stoichiometric complexes with CAND1 and cullins that can only be neddylated in the presence of a substrate adaptor. These CAND-cullin-DCNL complexes might represent 'reserve' CRLs that can be rapidly activated when needed. We further found that all DCNLs interact with most cullin subtypes, but that they are probably responsible for the neddylation of different subpopulations of any given cullin. This is consistent with the fact that the subcellular localization of DCNLs in tissue culture cells differs and that they show unique tissue-specific expression patterns in mice. Thus, the specificity between DCNL-type NEDD8 E3 enzymes and their cullin substrates is only apparent in well-defined physiological contexts and related to their subcellular distribution and restricted expression.
authors.affiliation: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Keuss
authors.affiliation: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Yann
authors.initials: Y
authors.lastname: Thomas
authors.affiliation: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Mcarthur
authors.affiliation: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Nicola T
authors.initials: NT
authors.lastname: Wood
authors.affiliation: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Axel
authors.initials: A
authors.lastname: Knebel
authors.affiliation: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK thimo.kurz@glasgow.ac.uk.
authors.forename: Thimo
authors.initials: T
authors.lastname: Kurz
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D044842:Cullin Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000075687:NEDD8 Protein; D015513:Oncogene Proteins / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: C486317:CAND1 protein, human; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; C408631:DCUN1D1 protein, human; C534519:DCUN1D3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014452:Ubiquitins; C584471:CULL-RING ligase, human; D044767:Ubiquitin-Protein Ligases; C000591617:DCUN1D5 protein, human; D010453:Peptide Synthases
keywords: CRL; Cullin-RING ligases; DCUN1D; NEDD8; SCCRO; Ubiquitin