Contents 1 Cullin-RING ubiquitin ligases 2 Modification by NEDD8 3 References 4 External links


Cullin-RING ubiquitin ligases[edit] Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms.[2] The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as CUL9, also known as p53 cytoplasmic anchor PARC, and the ANAPC2 subunit of the anaphase-promoting complex/cyclosome; both CUL9 and ANAPC2 have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins.[3][4][5]


Modification by NEDD8[edit] With the exception of ANAPC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Nedd8/Rub1 is a small ubiquitin-like protein, which was originally found to be conjugated to Cdc53, a cullin component of the SCF (Skp1-Cdc53/CUL1-F-box protein) E3 Ub ligase complex in Saccharomyces cerevisiae (Baker's yeast), and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue.[6]


References[edit] ^ [1] ^ Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM (June 1996). "cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family". Cell. 85 (6): 829–39. doi:10.1016/S0092-8674(00)81267-2. PMID 8681378.  ^ Petroski MD, Deshaies RJ (January 2005). "Function and regulation of cullin-RING ubiquitin ligases". Nat. Rev. Mol. Cell Biol. 6 (1): 9–20. doi:10.1038/nrm1547. PMID 15688063.  ^ Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP (April 2002). "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature. 416 (6882): 703–9. doi:10.1038/416703a. PMID 11961546.  ^ Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N (November 2004). "Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases". Cell. 119 (4): 517–28. doi:10.1016/j.cell.2004.10.019. PMID 15537541.  ^ Pan ZQ, Kentsis A, Dias DC, Yamoah K, Wu K (March 2004). "Nedd8 on cullin: building an expressway to protein destruction". Oncogene. 23 (11): 1985–97. doi:10.1038/sj.onc.1207414. PMID 15021886. 


External links[edit] Cullin family[permanent dead link] - Sanger Institute website. Cullin Proteins at the US National Library of Medicine Medical Subject Headings (MeSH) v t e Cell cycle proteins Cyclin A (A1, A2) B (B1, B2, B3) D (D1, D2, D3) E (E1, E2) CDK 1 2 3 4 5 6 7 8 9 10 CDK-activating kinase CDK inhibitor INK4a/ARF (p14arf/p16, p15, p18, p19) cip/kip (p21, p27, p57) P53 p63 p73 family p53 p63 p73 Other Cdc2 Cdc25 Cdc42 Cellular apoptosis susceptibility protein E2F Maturation promoting factor Wee Cullin (CUL7) Phases and checkpoints Interphase G1 phase S phase G2 phase M phase Mitosis (Preprophase Prophase Prometaphase Metaphase Anaphase Telophase) Cytokinesis Cell cycle checkpoints Restriction point Spindle checkpoint Postreplication checkpoint Other cellular phases Apoptosis G0 phase Meiosis v t e Enzymes: CO CS and CN ligases (EC 6.1-6.3) 6.1: Carbon-Oxygen Aminoacyl tRNA synthetase Alanine Arginine Asparagine Aspartate Cysteine D-alanine—poly(phosphoribitol) ligase Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine 6.2: Carbon-Sulfur Succinyl coenzyme A synthetase Acetyl—CoA synthetase Long-chain-fatty-acid—CoA ligase 6.3: Carbon-Nitrogen Glutamine synthetase Ubiquitin ligase Cullin Von Hippel–Lindau tumor suppressor UBE3A Mdm2 Anaphase-promoting complex UBR1 Glutathione synthetase CTP synthetase Adenylosuccinate synthase Argininosuccinate synthase Holocarboxylase synthetase GMP synthase Asparagine synthetase Carbamoyl phosphate synthetase I II Glutamate–cysteine ligase v t e Posttranslational modification Chaperones/ protein folding Heat shock proteins/ Chaperonins Hsp10/GroES Hsp27 Hsp47 HSP60/GroEL Hsp40/DnaJ A1 A2 A3 B1 B2 B11 B4 B6 B9 C1 C3 C5 C6 C7 C10 C11 C13 C14 C19 Hsp70 1A 1B 1L 2 4 4L 5 6 7 8 9 12A 14 Hsp90 α1 α2 β ER TRAP1 Other Alpha crystallin Clusterin Survival of motor neuron SMN1 SMN2 Protein targeting Signal peptide Mitochondrial targeting signal Ubiquitin E1 Ubiquitin-activating enzyme UBA1 UBA2 UBA3 UBA5 UBA6 UBA7 ATG7 NAE1 SAE1 E2 Ubiquitin-conjugating enzyme A B C D1 D2 D3 E1 E2 E3 G1 G2 H I J1 J2 K L1 L2 L3 L4 L6 M N O Q1 Q2 R1 (CDC34) R2 S V1 V2 Z E3 Ubiquitin ligase VHL Cullin CBL MDM2 FANCL UBR1 Deubiquitinating enzyme: Ataxin 3 USP6 CYLD ATG3 BIRC6 UFC1 Other Ubiquitin-like modifiers SUMO protein ISG15 URM1 NEDD8 FAT10 ATG8 ATG12 FUB1 MUB UFM1 UBL5 Prokaryotic ubiquitin-like protein This article incorporates text from the public domain Pfam and InterPro IPR001373 This article incorporates text from the public domain Pfam and InterPro IPR019559 This protein-related article is a stub. You can help Wikipedia by expanding it. v t e Retrieved from "https://en.wikipedia.org/w/index.php?title=Cullin&oldid=795600949" Categories: Protein familiesProtein stubsHidden categories: All articles with dead external linksArticles with dead external links from August 2017Articles with permanently dead external linksAll stub articles


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PfamInterProPROSITEStructural Classification Of ProteinsSUPERFAMILYPfamProtein Data BankPDBsumPfamInterProPfamProtein Data BankPDBsumProteinScaffoldUbiquitin LigaseRING Finger DomainCUL1SCF ComplexCUL2Elongin CCUL3CUL4ACUL4BCUL5CUL7CUL9ANAPC2Anaphase-promoting ComplexUbiquitinProtein ComplexUbiquitin LigaseProteinGlucoseDNA ReplicationCircadian RhythmsCatalyticEnzymeProteinCUL9P53CytoplasmPARC (gene)ANAPC2Protein-protein InteractionSignal Transducing Adaptor ProteinNEDD8ProteasomePolymerProtein ComplexSaccharomyces CerevisiaeCell CycleEmbryogenesisMetazoanSubstrate (biochemistry)NeddylationCovalentConserved SequenceLysineResidue (chemistry)Digital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed IdentifierWikipedia:Link RotSanger InstituteMedical Subject HeadingsTemplate:Cell Cycle ProteinsTemplate Talk:Cell Cycle ProteinsCell CycleProteinCyclinCyclin ACyclin A1Cyclin A2Cyclin BCyclin B1Cyclin B2Cyclin DCyclin D1Cyclin D2Cyclin D3Cyclin ECyclin E1Cyclin E2Cyclin-dependent KinaseCyclin-dependent Kinase 1Cyclin-dependent Kinase 2Cyclin-dependent Kinase 3Cyclin-dependent Kinase 4Cyclin-dependent Kinase 5Cyclin-dependent Kinase 6Cyclin-dependent Kinase 7Cyclin-dependent Kinase 8Cyclin-dependent Kinase 9Cyclin-dependent Kinase 10CDK-activating KinaseCyclin-dependent Kinase Inhibitor ProteinCell CycleP14arfP16CDKN2BCDKN2CCDKN2DCell CycleP21CDKN1BCyclin-dependent Kinase Inhibitor 1CP53 P63 P73 FamilyP53TP63P73Cdk1Cdc25CDC42Cellular Apoptosis Susceptibility ProteinE2FMaturation Promoting FactorWee1CUL7InterphaseG1 PhaseS PhaseG2 PhaseCell DivisionMitosisPreprophaseProphasePrometaphaseMetaphaseAnaphaseTelophaseCytokinesisCell Cycle CheckpointRestriction PointSpindle CheckpointPostreplication CheckpointApoptosisG0 PhaseMeiosisTemplate:Ligases CO CS And CNTemplate Talk:Ligases CO CS And CNEnzymeLigaseEnzyme Commission NumberList Of EC Numbers (EC 6)Aminoacyl TRNA SynthetaseAlanine—tRNA LigaseArginine—tRNA LigaseAsparagine—tRNA LigaseAspartate—tRNA LigaseCysteine—tRNA LigaseD-alanine—poly(phosphoribitol) LigaseGlutamate—tRNA LigaseGlutamine—tRNA LigaseGlycine—tRNA LigaseHistidine—tRNA LigaseIsoleucine—tRNA LigaseLeucine—tRNA LigaseLysine—tRNA LigaseMethionine—tRNA LigasePhenylalanine—tRNA LigaseProline—tRNA LigaseSerine—tRNA LigaseThreonine—tRNA LigaseTryptophan—tRNA LigaseTyrosine—tRNA LigaseValine—tRNA LigaseList Of EC Numbers (EC 6)Succinyl Coenzyme A SynthetaseAcetyl—CoA SynthetaseLong-chain-fatty-acid—CoA LigaseList Of EC Numbers (EC 6)Glutamine SynthetaseUbiquitin LigaseVon Hippel–Lindau Tumor SuppressorUBE3AMdm2Anaphase-promoting ComplexUBR1Glutathione SynthetaseCTP SynthetaseAdenylosuccinate SynthaseArgininosuccinate SynthaseHolocarboxylase SynthetaseGMP Synthase (glutamine—hydrolysing)Asparagine SynthetaseCarbamoyl Phosphate SynthetaseCarbamoyl Phosphate Synthetase ICarbamoyl Phosphate Synthase IIGlutamate–cysteine LigaseTemplate:Posttranslational ModificationTemplate Talk:Posttranslational ModificationPosttranslational ModificationChaperone (protein)Protein FoldingHeat Shock ProteinChaperoninGroESHsp27Heat Shock Protein 47HSP60GroELHsp40DNAJA1DNAJA2DNAJA3DNAJB1DNAJB2DNAJB11DNAJB4DNAJB6DNAJB9DNAJC1DNAJC3DNAJC5DNAJC6DNAJC7DNAJC10DNAJC11DNAJC13DNAJC14DNAJC19Hsp70HSPA1AHSPA1BHSPA1LHSPA2HSPA4HSPA4LBinding Immunoglobulin ProteinHSPA6HSPA7HSPA8HSPA9HSPA12AHSPA14Hsp90Heat Shock Protein 90kDa Alpha (cytosolic), Member A1HSP90AA2HSP90AB1HSP90B1TRAP1Alpha CrystallinClusterinSurvival Of Motor NeuronSMN1SMN2Protein TargetingSignal PeptideTarget PeptideUbiquitinUbiquitin-activating EnzymeUBE1SAE2UBE1CUBE1DC1UBE1L2UBE1LATG7APPBP1SAE1Ubiquitin-conjugating EnzymeUBE2AUBE2BUBE2CUBE2D1UBE2D2UBE2D3UBE2E1UBE2E2UBE2E3UBE2G1UBE2G2UBE2HUBE2IUBE2J1UBE2L3UBE2L6UBE2MUBE2NUBE2OCDC34UBE2R2UBE2V1UBE2V2UBE2ZUbiquitin LigaseVon Hippel–Lindau Tumor SuppressorCBL (gene)Mdm2FANCLUBR1Deubiquitinating EnzymeAtaxin 3USP6CYLD (gene)BIRC6UbiquitinSUMO ProteinISG15URM1NEDD8FAT10ATG8ATG12UFM1UBL5Prokaryotic Ubiquitin-like ProteinPublic DomainPfamInterProPublic DomainPfamInterProProteinWikipedia:StubTemplate:Protein-stubTemplate Talk:Protein-stubHelp:CategoryCategory:Protein FamiliesCategory:Protein StubsCategory:All Articles With Dead External LinksCategory:Articles With Dead External Links From August 2017Category:Articles With Permanently Dead External LinksCategory:All Stub ArticlesDiscussion About Edits From This IP Address [n]A List Of Edits Made From This IP Address [y]View The Content Page [c]Discussion About The Content Page [t]Edit This Page [e]Visit The Main Page [z]Guides To Browsing WikipediaFeatured Content – The Best Of WikipediaFind Background Information On Current EventsLoad A Random Article [x]Guidance On How To Use And Edit WikipediaFind Out About WikipediaAbout The Project, What You Can Do, Where To Find ThingsA List Of Recent Changes In The Wiki [r]List Of All 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