Gene Symbol: Cul1
Description: cullin 1
Alias: cullin-1, CUL-1
Species: human
Products:     Cul1

Top Publications

  1. Wu G, Xu G, Schulman B, Jeffrey P, Harper J, Pavletich N. Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase. Mol Cell. 2003;11:1445-56 pubmed
  2. Yamoah K, Oashi T, Sarikas A, Gazdoiu S, Osman R, Pan Z. Autoinhibitory regulation of SCF-mediated ubiquitination by human cullin 1's C-terminal tail. Proc Natl Acad Sci U S A. 2008;105:12230-5 pubmed publisher
    SCF (Skp1 x CUL1 x F-box protein x ROC1) E3 ubiquitin ligase and Cdc34 E2-conjugating enzyme catalyze polyubiquitination in a precisely regulated fashion...
  3. Shaik S, Nucera C, Inuzuka H, Gao D, Garnaas M, Frechette G, et al. SCF(?-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. J Exp Med. 2012;209:1289-307 pubmed publisher
    ..These results provide a new biomarker that may aid a rational use of tyrosine kinase inhibitors to treat refractory PTC. ..
  4. Dias D, Dolios G, Wang R, Pan Z. CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proc Natl Acad Sci U S A. 2002;99:16601-6 pubmed
    ..It is widely accepted that an F-box protein directs substrate ubiquitination within a Skp1.CUL1.F-box protein.ROC1 (SCF-ROC1) E3 ubiquitin ligase complex...
  5. Vashisht A, Zumbrennen K, Huang X, Powers D, Durazo A, Sun D, et al. Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science. 2009;326:718-21 pubmed publisher
    ..We found that a SKP1-CUL1-FBXL5 ubiquitin ligase protein complex associates with and promotes the iron-dependent ubiquitination and ..
  6. Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge S, et al. SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 2003;17:3062-74 pubmed
    ..These data indicate that Cdc25A turnover is more complex than previously appreciated and suggest roles for an additional kinase(s) in Chk1-dependent Cdc25A turnover. ..
  7. Kim A, Bommelje C, Lee B, Yonekawa Y, Choi L, Morris L, et al. SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation. J Biol Chem. 2008;283:33211-20 pubmed publisher
    ..We also show that SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin ..
  8. Michel J, Xiong Y. Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A. Cell Growth Differ. 1998;9:435-49 pubmed
    ..We have found that human cullin 1, but not the other closely related cullins 2, 3, 4A, and 5, selectively interacts with human SKP1...
  9. Busino L, Millman S, Scotto L, Kyratsous C, Basrur V, O CONNOR O, et al. Fbxw7?- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nat Cell Biol. 2012;14:375-85 pubmed publisher
    Fbxw7? is a member of the F-box family of proteins, which function as the substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes...

More Information


  1. Goldenberg S, Cascio T, Shumway S, Garbutt K, Liu J, Xiong Y, et al. Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Cell. 2004;119:517-28 pubmed
    ..Cand1, a 120 kDa HEAT repeat protein, forms a tight complex with the Cul1-Roc1 SCF catalytic core, inhibiting the assembly of the multisubunit E3 complex...
  2. Wu K, Yamoah K, Dolios G, Gan Erdene T, Tan P, Chen A, et al. DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. J Biol Chem. 2003;278:28882-91 pubmed
    ..Interestingly, DEN1 deconjugates cullin 1 (CUL1)-Nedd8 in a concentration-dependent manner...
  3. Pierce N, Lee J, Liu X, Sweredoski M, Graham R, Larimore E, et al. Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins. Cell. 2013;153:206-15 pubmed publisher
    ..Binding and ubiquitylation assays show that Cand1 is a protein exchange factor that accelerates the rate at which Cul1-Rbx1 equilibrates with multiple F box protein-Skp1 modules...
  4. Read M, Brownell J, Gladysheva T, Hottelet M, Parent L, Coggins M, et al. Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha. Mol Cell Biol. 2000;20:2326-33 pubmed
    ..These observations provide a functional link between the highly related ubiquitin and Nedd8 pathways of protein modification and show how they operate together to selectively target the signal-dependent degradation of IkappaBalpha. ..
  5. Yang C, Yu C, Chuang H, Chang C, Chang G, Yao T, et al. FBW2 targets GCMa to the ubiquitin-proteasome degradation system. J Biol Chem. 2005;280:10083-90 pubmed
    ..We found that SKP1 and CUL1, two key components of the SCF complex, associate with hGCMa in vivo...
  6. Kim J, Kim J, Kim D, Ryu G, Bae S, Seo Y. SCFhFBH1 can act as helicase and E3 ubiquitin ligase. Nucleic Acids Res. 2004;32:2287-97 pubmed
    ..previous study, we found that a human F-box DNA helicase, named hFBH1, interacted with SKP1 to form an SCF (SKP1-Cul1-F-box protein) complex together with CUL1 and ROC1 in an F-box-dependent manner...
  7. Lisztwan J, Marti A, Sutterlüty H, Gstaiger M, Wirbelauer C, Krek W. Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway. EMBO J. 1998;17:368-83 pubmed
    ..The dependency of p45(SKP2)-p19(SKP1) complex formation on cyclin A-CDK2 may ensure tight coordination of the activities of the cell cycle clock with those of a potential ubiquitin conjugation pathway. ..
  8. Chew E, Poobalasingam T, Hawkey C, Hagen T. Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells--evidence for cullin dimerization. Cell Signal. 2007;19:1071-80 pubmed
    ..We also provide evidence that Cul1 and Cul3, as well as their associated substrate recognition subunits Skp2 and Keap1, respectively, homooligomerize ..
  9. Suzuki H, Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M, et al. Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination. J Biol Chem. 2000;275:2877-84 pubmed
    ..These results indicate that not only betaTrCP1 but also betaTrCP2 participates in the ubiquitination-dependent destruction of IkappaBalpha by forming SCF(betaTrCP1-betaTrCP1) and SCF(betaTrCP2-betaTrCP2) ubiquitin-ligase complexes. ..
  10. Winston J, Strack P, Beer Romero P, Chu C, Elledge S, Harper J. The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes Dev. 1999;13:270-83 pubmed
    ..Our results suggest that an SCFbeta-TRCP complex functions in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway. ..
  11. Kipreos E, Lander L, Wing J, He W, Hedgecock E. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Cell. 1996;85:829-39 pubmed
    ..cul-1 represents a conserved family of genes, designated cullins, with at least five members in nematodes, six in humans, and three in budding yeast. ..
  12. Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, et al. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell. 2010;18:147-59 pubmed publisher
    ..Our results provide insight into the signaling pathways controlling Mdm2 destruction and further suggest that compromised regulation of Mdm2 results in attenuated p53 activity, thereby facilitating tumor progression. ..
  13. Oshikawa K, Matsumoto M, Yada M, Kamura T, Hatakeyama S, Nakayama K. Preferential interaction of TIP120A with Cul1 that is not modified by NEDD8 and not associated with Skp1. Biochem Biophys Res Commun. 2003;303:1209-16 pubmed
    The SCF complex, which consists of the invariable components Skp1, Cul1, and Rbx1 as well as a variable F-box protein, functions as an E3 ubiquitin ligase...
  14. Guardavaccaro D, Frescas D, Dorrello N, Peschiaroli A, Multani A, Cardozo T, et al. Control of chromosome stability by the beta-TrCP-REST-Mad2 axis. Nature. 2008;452:365-9 pubmed publisher
    ..The high levels of REST or its truncated variants found in certain human tumours may contribute to cellular transformation by promoting genomic instability. ..
  15. Sundqvist A, Liu G, Mirsaliotis A, Xirodimas D. Regulation of nucleolar signalling to p53 through NEDDylation of L11. EMBO Rep. 2009;10:1132-9 pubmed publisher
    ..By controlling the correct localization and stability of L11, NEDD8 acts as a crucial, new regulator of nucleolar signalling to p53. ..
  16. Sakata E, Yamaguchi Y, Miyauchi Y, Iwai K, Chiba T, Saeki Y, et al. Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity. Nat Struct Mol Biol. 2007;14:167-8 pubmed
    ..Our data imply that NEDD8 forms an active platform on the SCF complex for selective recruitment of ubiquitin-charged E2s in collaboration with RBX1, and thereby upregulates the E3 activity. ..
  17. Liu J, Furukawa M, Matsumoto T, Xiong Y. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Mol Cell. 2002;10:1511-8 pubmed
    ..We show here that p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation. CAND1 formed a ternary complex with CUL1 and ROC1...
  18. Gao D, Inuzuka H, Tan M, Fukushima H, Locasale J, Liu P, et al. mTOR drives its own activation via SCF(?TrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Mol Cell. 2011;44:290-303 pubmed publisher
  19. Saiga T, Fukuda T, Matsumoto M, Tada H, Okano H, Okano H, et al. Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development. Mol Cell Biol. 2009;29:3529-43 pubmed publisher
    ..Fbxo45 was found not to form an SCF complex as a result of an amino acid substitution in the consensus sequence for Cul1 binding...
  20. Min K, Hwang J, Lee J, Park Y, Tamura T, Yoon J. TIP120A associates with cullins and modulates ubiquitin ligase activity. J Biol Chem. 2003;278:15905-10 pubmed
    ..TIP120A formed a complex with CUL1 and Rbx1, but interfered with the binding of Skp1 and F-box proteins to CUL1...
  21. Kelsall I, Duda D, Olszewski J, Hofmann K, Knebel A, Langevin F, et al. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J. 2013;32:2848-60 pubmed publisher
    ..Cumulatively, our work proposes a conserved mechanism of CRL-induced Ariadne RBR ligase activation and further suggests a reciprocal role of this special class of RBRs as regulators of distinct CRLs. ..
  22. Carrano A, Eytan E, Hershko A, Pagano M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol. 1999;1:193-9 pubmed
    ..Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation. ..
  23. Bornstein G, Ganoth D, Hershko A. Regulation of neddylation and deneddylation of cullin1 in SCFSkp2 ubiquitin ligase by F-box protein and substrate. Proc Natl Acad Sci U S A. 2006;103:11515-20 pubmed
    ..We examined this problem for the case of SCF(Skp2), a cullin1 (Cul1)-containing ubiquitin ligase complex that contains the S phase-associated protein Skp2 as the substrate-binding F-..
  24. Nagahama H, Minamishima Y, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, et al. Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J. 2000;19:2069-81 pubmed
  25. Xirodimas D, Sundqvist A, Nakamura A, Shen L, Botting C, Hay R. Ribosomal proteins are targets for the NEDD8 pathway. EMBO Rep. 2008;9:280-6 pubmed publisher
    ..We further show that the lack of NEDDylation in cells causes ribosomal protein instability. Our studies identify a novel and specific role of the NEDD8 pathway in protecting a subset of ribosomal proteins from destabilization. ..
  26. Min K, Kwon M, Park H, Park Y, Yoon S, Yoon J. CAND1 enhances deneddylation of CUL1 by COP9 signalosome. Biochem Biophys Res Commun. 2005;334:867-74 pubmed
    ..Recent reports have suggested that CAND1, which specifically binds to unmodified CUL1 but not to neddylated one, is required for the in vivo function of SCFs, the CUL1-containing CRLs...
  27. Yang X, Menon S, Lykke Andersen K, Tsuge T, Di Xiao -, Wang X, et al. The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase progression via deneddylation of SCF Cul1. Curr Biol. 2002;12:667-72 pubmed highly dynamic, that its equilibrium can be effectively modulated by CSN, and that neddylation allows Cul1 to form larger protein complexes...
  28. den Besten W, Verma R, Kleiger G, Oania R, Deshaies R. NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway. Nat Struct Mol Biol. 2012;19:511-6, S1 pubmed publisher
    ..These results uncover an unexpected and conserved role for NEDD8 in linking CRL ubiquitin ligase function to the p97 pathway. ..
  29. Latres E, Chiaur D, Pagano M. The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene. 1999;18:849-54 pubmed
    ..human Fbp, beta-Trcp (beta-Transducin repeat containing protein), does indeed form a novel SCF with human Skp1 and Cul1. Consistent with recent reports indicating that Xenopus and Drosophila beta-Trcp homologs act as negative ..
  30. Wu K, Fuchs S, Chen A, Tan P, Gomez C, Ronai Z, et al. The SCF(HOS/beta-TRCP)-ROC1 E3 ubiquitin ligase utilizes two distinct domains within CUL1 for substrate targeting and ubiquitin ligation. Mol Cell Biol. 2000;20:1382-93 pubmed
    ..coordinated action of Cdc34 and the SCF(HOS/beta-TRCP)-ROC1 E3 ligase complex, comprised of four subunits (Skp1, cullin 1 [CUL1], HOS/beta-TRCP, and ROC1)...
  31. Chua Y, Boh B, Ponyeam W, Hagen T. Regulation of cullin RING E3 ubiquitin ligases by CAND1 in vivo. PLoS ONE. 2011;6:e16071 pubmed publisher
    ..However, only small amounts of CAND1 bind to Cul1 in cells, despite low basal levels of Cul1 neddylation and approximately equal cytoplasmic endogenous protein ..
  32. Ohki Y, Funatsu N, Konishi N, Chiba T. The mechanism of poly-NEDD8 chain formation in vitro. Biochem Biophys Res Commun. 2009;381:443-7 pubmed publisher
    ..In turn, ROC1 was essential for the transfer of poly-NEDD8 chain from Ubc12 to Cul-1. These results suggest the important regulatory role of ROC1 for poly-NEDD8 chain formation. ..
  33. Zhao J, Wei J, Mialki R, Mallampalli D, Chen B, Coon T, et al. F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation. Nat Immunol. 2012;13:651-8 pubmed publisher
    ..Our results suggest that modulation of the IL-33-ST2L axis by ubiquitin ligases might serve as a unique strategy for lessening pulmonary inflammation. ..
  34. Emberley E, Mosadeghi R, Deshaies R. 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. J Biol Chem. 2012;287:29679-89 pubmed publisher
    ..CSN is an efficient enzyme, with a k(cat) of ~1 s(-1) and K(m) for neddylated Cul1-Rbx1 of ~200 nm, yielding a k(cat)/K(m) near the anticipated diffusion-controlled limit...
  35. Zheng J, Yang X, Harrell J, Ryzhikov S, Shim E, Lykke Andersen K, et al. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell. 2002;10:1519-26 pubmed
    ..We report the isolation of a CUL1 binding protein, p120(CAND1)...
  36. Li Y, Hao B. Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem. 2010;285:13896-906 pubmed publisher
    The F-box proteins are the substrate recognition subunits of the SCF (Skp1-Cul1-Rbx1-F- box protein) ubiquitin ligase complexes that control the stability of numerous regulators in eukaryotic cells...
  37. D Angiolella V, Donato V, Vijayakumar S, Saraf A, Florens L, Washburn M, et al. SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature. 2010;466:138-42 pubmed publisher
    Generally, F-box proteins are the substrate recognition subunits of SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complexes, which mediate the timely proteolysis of important eukaryotic regulatory proteins...
  38. Sharon M, Mao H, Boeri Erba E, Stephens E, Zheng N, Robinson C. Symmetrical modularity of the COP9 signalosome complex suggests its multifunctionality. Structure. 2009;17:31-40 pubmed publisher
    ..This suggests that the propensity of the CSN complex to change and adapt its subunit composition might underlie its ability to perform multiple functions in vivo. ..
  39. Tan P, Fuchs S, Chen A, Wu K, Gomez C, Ronai Z, et al. Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. Mol Cell. 1999;3:527-33 pubmed
    ..ROC1, a novel SCF-associated protein, is recruited by cullin 1 to form a quatemary SCFHOS-ROC1 holenzyme (with Skp1 and the beta-TRCP homolog HOS)...
  40. Pick E, Golan A, Zimbler J, Guo L, Sharaby Y, Tsuge T, et al. The minimal deneddylase core of the COP9 signalosome excludes the Csn6 MPN- domain. PLoS ONE. 2012;7:e43980 pubmed publisher
    ..We propose that the budding yeast Csi1 is a functional equivalent of the canonical Csn6, and thus the composition of the CSN across phyla is more conserved than hitherto appreciated. ..
  41. Kawakami T, Chiba T, Suzuki T, Iwai K, Yamanaka K, Minato N, et al. NEDD8 recruits E2-ubiquitin to SCF E3 ligase. EMBO J. 2001;20:4003-12 pubmed
    ..This recruitment requires thioester linkage of Ub to Ubc4. Our findings indicate that the NEDD8-modifying system accelerates the formation of the E2-E3 complex, which stimulates protein polyubiquitylation. ..
  42. Duan S, Cermak L, Pagan J, Rossi M, Martinengo C, di Celle P, et al. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012;481:90-3 pubmed publisher
    ..Here we show that BCL6 is targeted for ubiquitylation and proteasomal degradation by a SKP1–CUL1–F-box protein (SCF) ubiquitin ligase complex that contains the orphan F-box protein FBXO11 (refs 5, 6)...
  43. Enchev R, Scott D, da Fonseca P, Schreiber A, Monda J, Schulman B, et al. Structural basis for a reciprocal regulation between SCF and CSN. Cell Rep. 2012;2:616-27 pubmed publisher
    Skp1-Cul1-Fbox (SCF) E3 ligases are activated by ligation to the ubiquitin-like protein Nedd8, which is reversed by the deneddylating Cop9 signalosome (CSN). However, CSN also promotes SCF substrate turnover through unknown mechanisms...
  44. Fukushima H, Ogura K, Wan L, Lu Y, Li V, Gao D, et al. SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Rep. 2013;4:803-16 pubmed publisher
  45. Kumar R, Neilsen P, Crawford J, McKirdy R, Lee J, Powell J, et al. FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex. Cancer Res. 2005;65:11304-13 pubmed
    ..We propose that FBXO31 functions as a tumor suppressor by generating SCF(FBXO31) complexes that target particular substrates, critical for the normal execution of the cell cycle, for ubiquitination and subsequent degradation. ..
  46. Li T, Pavletich N, Schulman B, Zheng N. High-level expression and purification of recombinant SCF ubiquitin ligases. Methods Enzymol. 2005;398:125-42 pubmed
    ..The SCF complexes are organized by the elongated scaffold protein subunit Cul1, which interacts with the Rbx1 RING finger protein at one end and the Skp1 adaptor protein at the other...
  47. Kleiger G, Saha A, Lewis S, Kuhlman B, Deshaies R. Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates. Cell. 2009;139:957-68 pubmed publisher
    ..rapid association driven by electrostatic interactions between the acidic tail of Cdc34 and a basic 'canyon' in the Cul1 subunit of SCF...
  48. Zhang Y, Otterness D, Chiang G, Xie W, Liu Y, Mercurio F, et al. Genotoxic stress targets human Chk1 for degradation by the ubiquitin-proteasome pathway. Mol Cell. 2005;19:607-18 pubmed
    ..The ubiquitination of Chk1 is mediated by E3 ligase complexes containing Cul1 or Cul4A...
  49. Chew E, Hagen T. Substrate-mediated regulation of cullin neddylation. J Biol Chem. 2007;282:17032-40 pubmed
    ..These ligases are composed of one of six mammalian cullin homologs (Cul1, Cul2, Cul3, Cul4a, Cul4b, and Cul5), the Ring finger containing protein Roc1/Rbx1, and cullin homolog-specific ..
  50. Zheng N, Schulman B, Song L, Miller J, Jeffrey P, Wang P, et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002;416:703-9 pubmed
    ..Here we present the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which shows that Cul1 is an elongated protein that consists of a long stalk and a ..
  51. Liu J, Wan L, Liu P, Inuzuka H, Liu J, Wang Z, et al. SCF(?-TRCP)-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway. Oncotarget. 2014;5:1026-37 pubmed
  52. Staropoli J, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron. 2003;37:735-49 pubmed
    ..Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. ..
  53. Morimoto M, Nishida T, Nagayama Y, Yasuda H. Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3 ligase and regulates its stability. Biochem Biophys Res Commun. 2003;301:392-8 pubmed
    SCF is a ubiquitin ligase and is composed of Skp1, Cul1, F-box protein, and Roc1. The catalytic site of the SCF is the Cul1/Roc1 complex and RING-finger protein Roc1...
  54. Hansen D, Loktev A, Ban K, Jackson P. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Mol Biol Cell. 2004;15:5623-34 pubmed
    ..These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase. ..
  55. Salahudeen A, Thompson J, Ruiz J, Ma H, Kinch L, Li Q, et al. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science. 2009;326:722-6 pubmed publisher
    ..These observations suggest a mechanistic link between iron sensing via the FBXL5 hemerythrin domain, IRP2 regulation, and cellular responses to maintain mammalian iron homeostasis. ..
  56. Kim J, Kim J, Lee S, Kim D, Kang H, Bae S, et al. The novel human DNA helicase hFBH1 is an F-box protein. J Biol Chem. 2002;277:24530-7 pubmed
    ..We demonstrate that hFBH1 is the first F-box protein that possesses intrinsic enzyme activity. The potential role of the F-box motif and the helicase activity of the enzyme are discussed with regard to regulation of DNA metabolism. ..
  57. Pick E, Lau O, Tsuge T, Menon S, Tong Y, Dohmae N, et al. Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes. Mol Cell Biol. 2007;27:4708-19 pubmed
    ..Overexpression of DET1 inhibits UV-induced CDT1 degradation in cultured cells. These findings demonstrate that the conserved DET1 complex modulates Cul4A functions by a novel mechanism. ..
  58. Seki A, Coppinger J, Du H, Jang C, Yates J, Fang G. Plk1- and beta-TrCP-dependent degradation of Bora controls mitotic progression. J Cell Biol. 2008;181:65-78 pubmed publisher
    ..We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression. ..
  59. Saha A, Deshaies R. Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation. Mol Cell. 2008;32:21-31 pubmed publisher
  60. Enchev R, Schreiber A, Beuron F, Morris E. Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3. Structure. 2010;18:518-27 pubmed publisher
    ..We compare the structure of CSN with its homologous complexes, the 26S proteasome lid and eIF3, and propose a conserved architecture implying similar assembly pathways and/or conserved substrate interaction modes. ..
  61. Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech Otschir D, et al. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003;22:1302-12 pubmed
    ..Curcumin treatment results in elevated amounts of c-Jun-Ub conjugates. We conclude that CK2 and PKD are recruited by CSN in order to regulate Ub conjugate formation. ..
  62. Lyapina S, Cope G, Serino G, Tsuge T, Zhou C, Wolf D, et al. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001;292:1382-5 pubmed
    ..To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and ..
  63. Busino L, Bassermann F, Maiolica A, Lee C, Nolan P, Godinho S, et al. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science. 2007;316:900-4 pubmed
    ..Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins. ..
  64. Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello N, et al. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature. 2003;426:87-91 pubmed
    ..Here we report that beta-TrCP is the F-box protein that targets phosphorylated Cdc25A for degradation by the Skp1/Cul1/F-box protein complex...
  65. Choo Y, Boh B, Lou J, Eng J, Leck Y, Anders B, et al. Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity. Mol Biol Cell. 2011;22:4706-15 pubmed publisher
    ..The deneddylating activity of CSN would subsequently promote its own dissociation to allow progression through the CRL activation cycle. ..
  66. Fuchs S, Chen A, Xiong Y, Pan Z, Ronai Z. HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene. 1999;18:2039-46 pubmed
    ..These results demonstrate that SCF(HOS) E3 ubiquitin ligase regulate both NF-kappaB and beta-catenin signaling pathways. ..
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    ..striking conformational rearrangements in the crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS analysis of NEDD8~Cul1(ctd)-Rbx1 relative to their unmodified counterparts...
  68. Schweitzer K, Bozko P, Dubiel W, Naumann M. CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha. EMBO J. 2007;26:1532-41 pubmed
    ..We propose that the CSN controls both CRL activity and stability of the CRL substrate IkappaBalpha. In consequence, basal and signal-induced CRL-dependent turnover of IkappaBalpha is precisely adapted to specific cellular needs. ..
  69. Zhong J, Shaik S, Wan L, Tron A, Wang Z, Sun L, et al. SCF ?-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration. Oncotarget. 2013;4:2339-53 pubmed
    ..Notably, depletion of either Cullin 1 or ?-TRCP1 led to increased levels of MTSS1...
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    ..The possible role of super-complexes composed of the CSN, the 26S proteasome and of Ub ligases in the regulation of protein stability is discussed. ..
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    b>Cul1, a member of the cullin ubiquitin ligase family, forms a multiprotein complex known as SCF and plays an essential role in numerous cellular and biological activities...
  73. Hwang J, Min K, Tamura T, Yoon J. TIP120A associates with unneddylated cullin 1 and regulates its neddylation. FEBS Lett. 2003;541:102-8 pubmed a negative regulator of a ubiquitin ligase by interfering with the binding of Skp1 and an F box protein to CUL1. Here we show that TIP120A binds to the unneddylated CUL1 but not the neddylated one...