{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:01:47Z","timestamp":1772172107227,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1005869","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000}}],"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T00:00:00Z","timestamp":1510876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Government of the People\u2019s Republic of China","award":["Foreign 1000 Talent Program"],"award-info":[{"award-number":["Foreign 1000 Talent Program"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM105802"],"award-info":[{"award-number":["GM105802"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA030199"],"award-info":[{"award-number":["CA030199"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM085764"],"award-info":[{"award-number":["GM085764"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM121834"],"award-info":[{"award-number":["GM121834"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005869","type":"journal-article","created":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T13:31:50Z","timestamp":1510925510000},"page":"e1005869","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Trade-off and flexibility in the dynamic regulation of the cullin-RING ubiquitin ligase repertoire"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-5376","authenticated-orcid":true,"given":"Ronny","family":"Straube","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meera","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietrich","family":"Flockerzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-1070","authenticated-orcid":true,"given":"Dieter A.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,11,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm1547","article-title":"Function and regulation of cullin-RING ubiquitin ligases","volume":"6","author":"MD Petroski","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-biochem-060310-170328","article-title":"The ubiquitin code","volume":"81","author":"D Kommander","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrc3700","article-title":"Roles of F-box proteins in cancer","volume":"14","author":"Z Wang","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2174\/1568009616666151112122231","article-title":"The SCF-type E3 ubiquitin ligases as cancer targets","volume":"16","author":"K Kitagawa","year":"2014","journal-title":"Curr Cancer Drug Targets"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e1006517","DOI":"10.1371\/journal.ppat.1006517","article-title":"Small molecule perturbation of the CAND1-CUL1-ubiquitin cycle stabilizes p53 and triggers Epstein-Barr virus reactivation","volume":"13","author":"N Tikhmyanova","year":"2017","journal-title":"PLoS Pathog"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0092-8674(00)80403-1","article-title":"F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex","volume":"91","author":"D Skowyra","year":"1997","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0092-8674(00)80404-3","article-title":"A complex of Cdc4p, Skp1p, and Cdc53p\/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p","volume":"91","author":"RM Feldman","year":"1997","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/embor.2013.173","article-title":"Building and remodelling cullin-RING E3 ubiquitin ligases","volume":"14","author":"JR Lydeard","year":"2013","journal-title":"EMBO Rep"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.cell.2010.11.017","article-title":"Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics","volume":"143","author":"EJ Bennett","year":"2010","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.cell.2013.02.024","article-title":"Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins","volume":"153","author":"NW Pierce","year":"2013","journal-title":"Cell"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.cell.2016.07.027","article-title":"Two distinct types of E3 ligases work in unison to regulate substrate ubiquitylation","volume":"166","author":"DC Scott","year":"2016","journal-title":"Cell"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1093\/emboj\/20.15.4003","article-title":"NEDD8 recruits E2-ubiquitin to SCF E3 ligase","volume":"20","author":"T Kawakami","year":"2001","journal-title":"EMBO J"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.cell.2008.07.022","article-title":"Structural insights into NEDD8 activation of cullin-RING ligases: Conformational control of conjugation","volume":"134","author":"DM Duda","year":"2008","journal-title":"Cell"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.molcel.2008.08.021","article-title":"Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation","volume":"32","author":"A Saha","year":"2008","journal-title":"Mol Cell"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1126\/science.1059780","article-title":"Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome","volume":"292","author":"S Lyapina","year":"2001","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nature17416","article-title":"Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome","volume":"531","author":"S Cavidini","year":"2016","journal-title":"Nature"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/ncomms2636","article-title":"CAND1 controls <italic>in vivo<\/italic> dynamics of the cullin 1-RING ubiquitin ligase repertoire","volume":"4","author":"S Wu","year":"2013","journal-title":"Nat Commun"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1038\/ncomms2628","article-title":"CSN- and CAND1-dependent remodelling of the budding yeast SCF complex","volume":"4","author":"A Zemla","year":"2013","journal-title":"Nat Commun"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/s00249-002-0225-3","article-title":"Exchange factors, effectors, GAPs and motor proteins: common thermodynamic and kinetic principles for different functions","volume":"31","author":"RS Goody","year":"2002","journal-title":"Eur Biophys J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/S1097-2765(02)00784-0","article-title":"CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex","volume":"10","author":"J Zheng","year":"2002","journal-title":"Mol Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1105\/tpc.021949","article-title":"<italic>Arabidopsis<\/italic> CAND1, un unmodified CUL1-interacting protein is involved in multiple developmental pathways controlled by ubiquitin\/proteasome-mediated protein degradation","volume":"16","author":"S Feng","year":"2004","journal-title":"Plant Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1105\/tpc.021923","article-title":"<italic>Arabidopsis<\/italic> ETA2, an apparent ortholog of the human cullin-interacting protein CAND1, is required for auxin responses mediated by the SCF(TIR1) ubiquitin ligase","volume":"16","author":"HW Chuang","year":"2004","journal-title":"Plant Cell"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1128\/MCB.26.4.1235-1244.2006","article-title":"CAND1-mediated substrate adaptor recycling is required for efficient repression of Nrf2 by Keap1","volume":"26","author":"SC Lo","year":"2006","journal-title":"Mol Cell Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.molcel.2009.07.024","article-title":"F-box-directed CRL complex assembly and regulation by the CSN and CAND1","volume":"35","author":"MW Schmidt","year":"2009","journal-title":"Mol Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"11515","DOI":"10.1073\/pnas.0603921103","article-title":"Regulation of neddylation and deneddylation of cullin1 in SCF<sup>Skp2<\/sup> ubiquitin ligase by F-box protein and substrate","volume":"103","author":"G Bornstein","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/S1097-2765(02)00783-9","article-title":"NEDD8 Modification of CUL1 dissociates p120<sup>CAND1<\/sup>, an inhibitor of CUL1-SKP1 binding and SCF ligases","volume":"10","author":"J Liu","year":"2002","journal-title":"Mol Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cell.2004.10.019","article-title":"Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases","volume":"119","author":"SJ Goldenberg","year":"2004","journal-title":"Cell"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1038\/emboj.2009.354","article-title":"Cullin neddylation and substrate-adaptors counteract SCF inhibition by the CAND1-like protein Lag2 in <italic>Saccharomyces cerevisiae<\/italic>","volume":"28","author":"E Siergiejuk","year":"2009","journal-title":"EMBO J"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0092-8674(00)80098-7","article-title":"SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box","volume":"86","author":"C Bai","year":"1996","journal-title":"Cell"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"29679","DOI":"10.1074\/jbc.M112.352484","article-title":"Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism","volume":"287","author":"ED Emberly","year":"2012","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.celrep.2012.08.019","article-title":"Structural basis for a reciprocal regulation between SCF and CSN","volume":"2","author":"RI Enchev","year":"2012","journal-title":"Cell Rep"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1046\/j.1365-2443.1998.00225.x","article-title":"Two F-box\/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase","volume":"3","author":"K Kominami","year":"1998","journal-title":"Genes Cells"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0960-9822(99)80165-1","article-title":"F-box\/WD-repeat proteins Pop1p and Sud1p\/Pop2p form complexes that bind and direct the proteolysis of Cdc18p","volume":"9","author":"DA Wolf","year":"1999","journal-title":"Curr Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"8159","DOI":"10.1073\/pnas.95.14.8159","article-title":"<italic>sud1(+)<\/italic> targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins for degradation and stops unwanted diploidization in fission yeast","volume":"95","author":"PV Jallepalli","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2091-3-22","article-title":"Combinatorial diversity of fission yeast SCF ubiquitin ligases by homo- and heterooligomeric assemblies of the F-box proteins Pop1p and Pop2p","volume":"3","author":"V Seibert","year":"2002","journal-title":"BMC Biochem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.biocel.2015.07.013","article-title":"CAND1 exchange factor promotes Keap1 integration into cullin 3-RING ubiquitin ligase during adipogenesis","volume":"66","author":"D Dubiel","year":"2015","journal-title":"Int J Biochem Cell Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"12543","DOI":"10.1021\/bi00039a008","article-title":"The kinetic mechanism of Ran-nucleotide exchange catalyzed by RCC1","volume":"34","author":"C Klebe","year":"1995","journal-title":"Biochem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1021\/bi015712w","article-title":"Kinetic mechanism of elongation factor Ts-catalyzed nucleotide exchange in elongation factor Tu","volume":"41","author":"KB Gromadski","year":"2002","journal-title":"Biochem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1016\/j.bpj.2010.10.013","article-title":"A combined molecular dynamics and rapid kinetics approach to identify conserved three-dimensional communication networks in elongation factor Tu","volume":"99","author":"HJ Wieden","year":"2010","journal-title":"Biophys J"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e172","DOI":"10.1371\/journal.pcbi.0020172","article-title":"Computational model explains high activity and rapid cycling of Rho GTPases within protein complexes","volume":"2","author":"AB Goryachev","year":"2006","journal-title":"PLoS Comp Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e0151861","DOI":"10.1371\/journal.pone.0151861","article-title":"Activation of G proteins by guanine nucleotide exchange factors relies on GTPase activity","volume":"11","author":"RJ Stanley","year":"2016","journal-title":"PLoS ONE"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1145\/779359.779362","article-title":"MATCONT: A MATLAB package for numerical bifurcation analysis of ODEs","volume":"29","author":"A Dhooge","year":"2003","journal-title":"ACM T Math Software"},{"key":"ref43","unstructured":"MATLAB 2015b. The MathWorks. Natick; 2015."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1005869","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T11:59:56Z","timestamp":1540209596000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005869"}},"subtitle":[],"editor":[{"given":"Vahid","family":"Shahrezaei","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,11,17]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005869","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/168898","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,17]]}}}