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.[3] 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 p53cytoplasmic 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.[4][5][6]
Modification by NEDD8edit
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 lysineresidue.[7]
Referencesedit
^Bosu, Dimple R.; Kipreos, Edward T. (2008). "Cullin-RING ubiquitin ligases: Global regulation and activation cycles". Cell Division. 3: 7. doi:10.1186/1747-1028-3-7. PMC2266742. PMID 18282298.
^Bruce, Alberts (2014-11-18). Molecular biology of the cell (Sixth ed.). New York, NY. ISBN9780815344322. OCLC 887605755.{{cite book}}: CS1 maint: location missing publisher (link)
^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. S2CID 15805562.
^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. Bibcode:2002Natur.416..703Z. doi:10.1038/416703a. PMID 11961546. S2CID 4423882.
^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. S2CID 1606360.
^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.
cullin, confused, with, cuillin, mountain, range, scotland, with, culin, family, hydrophobic, scaffold, proteins, which, provide, support, ubiquitin, ligases, eukaryotes, appear, have, cullins, they, combine, with, ring, proteins, form, ring, ubiquitin, ligase. Not to be confused with Cuillin a mountain range in Scotland or with Culin Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases E3 All eukaryotes appear to have cullins They combine with RING proteins to form Cullin RING ubiquitin ligases CRLs that are highly diverse and play a role in myriad cellular processes most notably protein degradation by ubiquitination 1 2 Cullinstructure of the cul1 rbx1 skp1 f boxskp2 scf ubiquitin ligase complexIdentifiersSymbolCullinPfamPF00888InterProIPR001373PROSITEPDOC00967SCOP21ldj SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryCullin protein neddylation domainstructure of the cul1 rbx1 skp1 f boxskp2 scf ubiquitin ligase complexIdentifiersSymbolCullin Nedd8PfamPF10557InterProIPR019559Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryThe human genome contains eight cullin genes CUL1 part of SCF complex CUL2 part of ECS complex Elongin C CUL2 SOCS box CUL3 part of CUL3 BTB complex CUL4A CUL4B CUL5 CUL7 CUL9 also known as PARCThere is also a more distant member called ANAPC2 or APC2 part of the Anaphase promoting complex CUL1 2 3 4A 4B 5 and 7 each form part of a multi subunit ubiquitin complex Contents 1 Cullin RING ubiquitin ligases 2 Modification by NEDD8 3 References 4 External linksCullin RING ubiquitin ligases editCullin 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 3 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 4 5 6 Modification by NEDD8 editWith 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 7 References edit Bosu Dimple R Kipreos Edward T 2008 Cullin RING ubiquitin ligases Global regulation and activation cycles Cell Division 3 7 doi 10 1186 1747 1028 3 7 PMC 2266742 PMID 18282298 Bruce Alberts 2014 11 18 Molecular biology of the cell Sixth ed New York NY ISBN 9780815344322 OCLC 887605755 a href Template Cite book html title Template Cite book cite book a CS1 maint location missing publisher link 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 S2CID 15805562 Petroski MD Deshaies RJ January 2005 Function and regulation of cullin RING ubiquitin ligases PDF Nat Rev Mol Cell Biol 6 1 9 20 doi 10 1038 nrm1547 PMID 15688063 S2CID 24159190 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 Bibcode 2002Natur 416 703Z doi 10 1038 416703a PMID 11961546 S2CID 4423882 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 S2CID 1606360 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 editCullin family Sanger Institute website Cullin Proteins at the U S National Library of Medicine Medical Subject Headings MeSH This article incorporates text from the public domain Pfam and InterPro IPR001373 This article incorporates text from the public domain Pfam and InterPro IPR019559 nbsp This protein related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Cullin amp oldid 1176310817, wikipedia, wiki, book, books, library,
