CUL3

Summary

Gene Symbol: CUL3
Description: cullin 3
Alias: CUL-3, PHA2E, cullin-3
Species: human
Products:     CUL3

Top Publications

  1. 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 in intact ..
  2. Shibata T, Ohta T, Tong K, Kokubu A, Odogawa R, Tsuta K, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008;105:13568-73 pubmed publisher
    ..circumstances, low cellular concentrations of Nrf2 are maintained by proteasomal degradation through a Keap1-Cul3-Roc1-dependent mechanism...
  3. He X, Chen M, Lin G, Ma Q. Arsenic induces NAD(P)H-quinone oxidoreductase I by disrupting the Nrf2 x Keap1 x Cul3 complex and recruiting Nrf2 x Maf to the antioxidant response element enhancer. J Biol Chem. 2006;281:23620-31 pubmed
    ..Arsenic stabilized Nrf2 protein, extending the t(1/2) of Nrf2 from 21 to 200 min by inhibiting the Keap1 x Cul3-dependent ubiquitination and proteasomal turnover of Nrf2...
  4. Ichikawa T, Li J, Meyer C, Janicki J, Hannink M, Cui T. Dihydro-CDDO-trifluoroethyl amide (dh404), a novel Nrf2 activator, suppresses oxidative stress in cardiomyocytes. PLoS ONE. 2009;4:e8391 pubmed publisher
    ..Dh404 interrupted the Keap1-Cul3-Rbx1 E3 ligase complex-mediated Nrf2 ubiquitination and subsequent degradation saturating the binding capacity of ..
  5. Baird L, Dinkova Kostova A. Diffusion dynamics of the Keap1-Cullin3 interaction in single live cells. Biochem Biophys Res Commun. 2013;433:58-65 pubmed publisher
    ..protein 1 (Keap1) targets Nrf2 for ubiquitination and proteasomal degradation via association with Cullin3 (Cul3)-based Rbx1 E3 ubiquitin ligase...
  6. Ohta A, Schumacher F, Mehellou Y, Johnson C, Knebel A, MacArtney T, et al. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. Biochem J. 2013;451:111-22 pubmed publisher
    ..Recent studies have identified Gordon's hypertension syndrome patients with mutations in either CUL3 (Cullin-3) or the BTB protein KLHL3 (Kelch-like 3)...
  7. Lo S, Hannink M. CAND1-mediated substrate adaptor recycling is required for efficient repression of Nrf2 by Keap1. Mol Cell Biol. 2006;26:1235-44 pubmed
    ..Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex to repress steady-state levels of Nrf2 and Nrf2-dependent transcription...
  8. Singer J, Gurian West M, Clurman B, Roberts J. Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. Genes Dev. 1999;13:2375-87 pubmed
  9. Nioi P, Nguyen T. A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity. Biochem Biophys Res Commun. 2007;362:816-21 pubmed
    Keap1 is the substrate recognition module of a Cullin 3-based E3 ubiquitin ligase. Its primary role is to catalyze the ubiquitylation of the Nrf2 transcription factor...

More Information

Publications66

  1. Kwon J, La M, Oh K, Oh Y, Kim G, Seol J, et al. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. J Biol Chem. 2006;281:12664-72 pubmed
    ..SPOP is a BTB (Bric-a-brac/Tramtrack/Broad complex) protein that constitutes Cul3-based ubiquitin ligases...
  2. Osawa M, Ogura Y, Isobe K, Uchida S, Nonoyama S, Kawaguchi H. CUL3 gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy. Pediatr Nephrol. 2013;28:1881-4 pubmed publisher
    ..Four genes responsible for pseudohypoaldosteronism type II (PHA-II) have been identified, thereby facilitating molecular diagnostic testing...
  3. Chen Y, Yang Z, Meng M, Zhao Y, Dong N, Yan H, et al. Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol Cell. 2009;35:841-55 pubmed publisher
    b>Cul3, a Cullin family scaffold protein, is thought to mediate the assembly of a large number of SCF (Skp1-Cullin1-F-box protein)-like ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors...
  4. Kigoshi Y, Tsuruta F, Chiba T. Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation. J Biol Chem. 2011;286:33613-21 pubmed publisher
    ..BTB proteins act as the substrate recognition subunit that recruits their cognate substrates to the Cullin 3-based multisubunit E3s...
  5. Eggler A, Small E, Hannink M, Mesecar A. Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. Biochem J. 2009;422:171-80 pubmed publisher
    ..ECH-associated protein 1) protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3 (cullin 3)-mediated ubiquitination complex...
  6. Cummings C, Bentley C, Perdue S, Baas P, Singer J. The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells. J Biol Chem. 2009;284:11663-75 pubmed publisher
    ..In seeking to elucidate additional biological roles for Cul3 we performed a two-hybrid screen and identified Ctb9/KLHDC5 as a Cul3-interacting protein...
  7. Sumara I, Peter M. A Cul3-based E3 ligase regulates mitosis and is required to maintain the spindle assembly checkpoint in human cells. Cell Cycle. 2007;6:3004-10 pubmed
    ..Here we present evidence that a Cul3-based E3 ubiquitin-ligase is required to maintain SAC signaling in human cells...
  8. 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
    ..In conclusion, our study suggests that CAND1 does not function by sequestering cullins in vivo to prevent substrate receptor autoubiquitination and is likely to regulate cullin RING ligase activity via alternative mechanisms. ..
  9. Moghe S, Jiang F, Miura Y, Cerny R, Tsai M, Furukawa M. The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A. Biol Open. 2012;1:82-91 pubmed publisher
    ..b>CUL3 targets its substrates through BTB proteins...
  10. Mori Y, Wakabayashi M, Mori T, Araki Y, Sohara E, Rai T, et al. Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through different molecular mechanisms. Biochem Biophys Res Commun. 2013;439:30-4 pubmed publisher
    Recently, we demonstrated that WNK4 is a substrate for KLHL3-Cullin3 (CUL3) E3 ubiquitin ligase complexes and that impaired WNK4 ubiquitination is a common mechanism for pseudohypoaldosteronism type II (PHAII) caused by WNK4, KLHL3, and ..
  11. 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 adaptor and ..
  12. Beck J, Maerki S, Posch M, Metzger T, Persaud A, Scheel H, et al. Ubiquitylation-dependent localization of PLK1 in mitosis. Nat Cell Biol. 2013;15:430-9 pubmed publisher
    ..Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and ..
  13. Furukawa M, Ohta T, Xiong Y. Activation of UBC5 ubiquitin-conjugating enzyme by the RING finger of ROC1 and assembly of active ubiquitin ligases by all cullins. J Biol Chem. 2002;277:15758-65 pubmed
    ..We suggest that RING-E2, rather than cullin-RING, constitutes the catalytic core of the ubiquitin ligase and that one major function of the cullin subunit is to assemble the RING-E2 catalytic core and substrates together. ..
  14. Angers S, Thorpe C, Biechele T, Goldenberg S, Zheng N, MacCoss M, et al. The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. Nat Cell Biol. 2006;8:348-57 pubmed
  15. Shen H, Korutla L, Champtiaux N, Toda S, LaLumiere R, Vallone J, et al. NAC1 regulates the recruitment of the proteasome complex into dendritic spines. J Neurosci. 2007;27:8903-13 pubmed
    ..These experiments show that NAC1 modulates the translocation of the UPS from the nucleus into dendritic spines, thereby suggesting a potential missing link in the recruitment of necessary proteolysis machinery for synaptic remodeling. ..
  16. 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
    ..These observations thus suggest that TIP120A may function as a negative regulator of the SCF complex by binding to nonneddylated Cul1 and thereby preventing assembly of this ubiquitin ligase. ..
  17. Bunce M, Boronenkov I, Anderson R. Coordinated activation of the nuclear ubiquitin ligase Cul3-SPOP by the generation of phosphatidylinositol 5-phosphate. J Biol Chem. 2008;283:8678-86 pubmed publisher
    ..and SPOP (speckle-type POZ domain protein), a nuclear speckle-associated protein that recruits substrates to Cul3-based ubiquitin ligases...
  18. Boyden L, Choi M, Choate K, Nelson Williams C, Farhi A, Toka H, et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012;482:98-102 pubmed publisher
    ..Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families...
  19. Cullinan S, Gordan J, Jin J, Harper J, Diehl J. The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol Cell Biol. 2004;24:8477-86 pubmed
    ..We demonstrate that Keap1 is not solely a cytosolic anchor; rather, Keap1 is an adaptor that bridges Nrf2 to Cul3. We demonstrate that Cul3-Keap1 complexes regulate Nrf2 polyubiquitination both in vitro and in vivo...
  20. Berthold J, Schenkova K, Ramos S, Miura Y, Furukawa M, Aspenstrom P, et al. Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes--evidence for an autoregulatory mechanism. Exp Cell Res. 2008;314:3453-65 pubmed publisher
    ..RhoBTB proteins, RhoBTB1 and RhoBTB2, have been proposed as tumor suppressors and might function as adaptors of Cul3-dependent ubiquitin ligase complexes...
  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. Wu G, Peng J. Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. FEBS Lett. 2013;587:1717-22 pubmed publisher
    ..The effect of KLHL3 on WNK4 degradation was blocked by a dominant negative form of cullin 3. All five PHAII mutations of KLHL3 tested disrupted the regulation on WNK4...
  23. Canning P, Cooper C, Krojer T, Murray J, Pike A, Chaikuad A, et al. Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases. J Biol Chem. 2013;288:7803-14 pubmed publisher
    ..b>Cul3-based Cullin-RING ligases are uniquely associated with BTB adaptors that incorporate homodimerization, Cul3 ..
  24. Errington W, Khan M, Bueler S, Rubinstein J, Chakrabartty A, Prive G. Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase. Structure. 2012;20:1141-53 pubmed publisher
    ..structure of the E3 ligase adaptor protein SPOP (speckle-type POZ protein) in complex with the N-terminal domain of Cul3 at 2.4 Å resolution...
  25. Correale S, Pirone L, Di Marcotullio L, De Smaele E, Greco A, Mazzà D, et al. Molecular organization of the cullin E3 ligase adaptor KCTD11. Biochimie. 2011;93:715-24 pubmed publisher
    ..Indeed, sKCTD11 presents an incomplete POZ/BTB domain. Nonetheless, sKCTD11 is still able to bind Cul3, although to much lesser extent than lKCTD11, and to perform its biological activity...
  26. Kaspar J, Jaiswal A. An autoregulatory loop between Nrf2 and Cul3-Rbx1 controls their cellular abundance. J Biol Chem. 2010;285:21349-58 pubmed publisher
    The INrf2 (Keap1)/Cul3-Rbx1 complex constantly degrades Nrf2 under normal conditions. When a cell encounters oxidative or electrophilic stress, Nrf2 dissociates from the INrf2/Cul3-Rbx1 complex and translocates into the nucleus...
  27. Rachakonda G, Xiong Y, Sekhar K, Stamer S, Liebler D, Freeman M. Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3. Chem Res Toxicol. 2008;21:705-10 pubmed publisher
    ..is mediated by the transcription factor NF-E2-related factor 2 (Nrf2), which, in turn, is regulated by CUL-E3 (CUL3) ligase-mediated ubiquitylation...
  28. McMahon M, Thomas N, Itoh K, Yamamoto M, Hayes J. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. J Biol Chem. 2006;281:24756-68 pubmed
    ..We now report that it is as a homodimer that the substrate adaptor Keap1 interacts with Cul3. The resulting complex facilitates ubiquitylation of the Nrf2 transcription factor but only when this substrate ..
  29. Rondou P, Haegeman G, Vanhoenacker P, Van Craenenbroeck K. BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase. J Biol Chem. 2008;283:11083-96 pubmed publisher
  30. Huotari J, Meyer Schaller N, Hubner M, Stauffer S, Katheder N, Horvath P, et al. Cullin-3 regulates late endosome maturation. Proc Natl Acad Sci U S A. 2012;109:823-8 pubmed publisher
    Cullin-3 (Cul3) functions as a scaffolding protein in the Bric-a-brac, Tramtrack, Broad-complex (BTB)-Cul3-Rbx1 ubiquitin E3 ligase complex. Here, we report a previously undescribed role for Cul3 complexes in late endosome (LE) maturation...
  31. Ji A, Privé G. Crystal structure of KLHL3 in complex with Cullin3. PLoS ONE. 2013;8:e60445 pubmed publisher
    KLHL3 is a BTB-BACK-Kelch family protein that serves as a substrate adapter in Cullin3 (Cul3) E3 ubiquitin ligase complexes...
  32. 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
    ..These results suggest that TIP120A functions as a negative regulator of SCF E3 ubiquitin ligases and may modulate other cullin ligases in a similar fashion. ..
  33. Furukawa M, Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol. 2005;25:162-71 pubmed
    ..b>Cullin 3 (Cul3), but not other cullins, binds directly with BTB domains to constitute a potentially large number of BTB-..
  34. Bayon Y, Trinidad A, de la Puerta M, del Carmen Rodríguez M, Bogetz J, Rojas A, et al. KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases. FEBS J. 2008;275:3900-10 pubmed publisher
    ..These findings suggest that KCTD5 is a substrate-specific adaptor for cullin3-based E3 ligases. ..
  35. Lee Y, Yuan W, Ho H, Chen C, Shih H, Chen R. The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses. EMBO J. 2010;29:1748-61 pubmed publisher
    ..Here, we identify the BTB-Kelch protein KLHL20 as a negative regulator of DAPK. KLHL20 binds DAPK and Cullin 3 (Cul3) via its Kelch-repeat domain and BTB domain, respectively...
  36. Zhuang M, Calabrese M, Liu J, Waddell M, Nourse A, Hammel M, et al. Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol Cell. 2009;36:39-50 pubmed publisher
    In the largest E3 ligase subfamily, Cul3 binds a BTB domain, and an associated protein-interaction domain such as MATH recruits substrates for ubiquitination...
  37. Lee D, Kuo H, Liu M, Chou C, Xia W, Du Y, et al. KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta. Mol Cell. 2009;36:131-40 pubmed publisher
    ..Here, we show that a Cullin 3 (CUL3)-based ubiquitin ligase, Kelch-like ECH-associated protein 1 (KEAP1), is responsible for IKKbeta ..
  38. Maerki S, Olma M, Staubli T, Steigemann P, Gerlich D, Quadroni M, et al. The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis. J Cell Biol. 2009;187:791-800 pubmed publisher
    b>Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis...
  39. Zhang D, Lo S, Cross J, Templeton D, Hannink M. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol. 2004;24:10941-53 pubmed
    ..In this report, we demonstrate that Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex...
  40. Du M, Sansores Garcia L, Zu Z, Wu K. Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family. J Biol Chem. 1998;273:24289-92 pubmed
    ..Hs-CUL-3 widely expressed in human tissues and its expression in cultured COLO205 colon cancer cells was increased when compared with that in normal colon cells. It is likely that Hs-CUL-3 is involved in cell proliferation control. ..
  41. Jin L, Pahuja K, Wickliffe K, Gorur A, Baumgärtel C, Schekman R, et al. Ubiquitin-dependent regulation of COPII coat size and function. Nature. 2012;482:495-500 pubmed publisher
    ..Here, we identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat formation...
  42. Huang X, Hetfeld B, Seifert U, Kahne T, Kloetzel P, Naumann M, et al. Consequences of COP9 signalosome and 26S proteasome interaction. FEBS J. 2005;272:3909-17 pubmed
    ..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. ..
  43. Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, et al. Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension. Cell Rep. 2013;3:858-68 pubmed publisher
    ..Thus, WNK4 is a target for KLHL3-mediated ubiquitination, and the impaired ubiquitination of WNK4 is a common mechanism of human hereditary hypertension...
  44. Sumara I, Quadroni M, Frei C, Olma M, Sumara G, Ricci R, et al. A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. Dev Cell. 2007;12:887-900 pubmed
    Faithful cell-cycle progression is tightly controlled by the ubiquitin-proteasome system. Here we identify a human Cullin 3-based E3 ligase (Cul3) which is essential for mitotic division...
  45. Kobayashi A, Kang M, Okawa H, Ohtsuji M, Zenke Y, Chiba T, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol. 2004;24:7130-9 pubmed
    ..Indeed, Cullin 3 (Cul3), a subunit of the E3 ligase complex, was found to interact specifically with Keap1 in vivo...
  46. Hernández Muñoz I, Lund A, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, et al. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci U S A. 2005;102:7635-40 pubmed
    ..We further demonstrate that MACROH2A1 deposition is regulated by the CULLIN3/SPOP ligase complex and is actively involved in stable X inactivation, likely through the formation of an additional layer of epigenetic silencing. ..
  47. 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
    ..Our data suggest that enhancement of CSN-mediated deneddylation by CAND1 may contribute to its function as a positive regulator of SCFs in vivo. ..
  48. Pelham C, Ketsawatsomkron P, Groh S, Grobe J, de Lange W, Ibeawuchi S, et al. Cullin-3 regulates vascular smooth muscle function and arterial blood pressure via PPAR? and RhoA/Rho-kinase. Cell Metab. 2012;16:462-72 pubmed publisher
    ..We conclude that Cullin-3 regulates vascular function and arterial pressure, thus providing a mechanistic link between mutations in Cullin-3 and hypertension in humans. ..
  49. Yuan W, Lee Y, Huang S, Lin Y, Chen T, Chung H, et al. A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression. Cancer Cell. 2011;20:214-28 pubmed publisher
    ..Here, we show that KLHL20, a Cullin3 (Cul3) substrate adaptor induced by HIF-1, coordinates with the actions of CDK1/2 and Pin1 to mediate hypoxia-induced PML ..
  50. 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
    ..Disruption of the Ubx5 UIM results in a loss of CRL binding and consequently impedes degradation of a Cul3 substrate...
  51. 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
  52. Shibata S, Zhang J, Puthumana J, Stone K, Lifton R. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. Proc Natl Acad Sci U S A. 2013;110:7838-43 pubmed publisher
    ..Recently, mutations in Kelch-like 3 (KLHL3) and Cullin 3 (CUL3), components of an E3 ubiquitin ligase complex, were found to cause PHAII, suggesting that loss of this ..
  53. 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
    ..CSN also did not affect recruitment of the substrate-receptor SPOP to Cul3, suggesting it may not function to facilitate the exchange of Cul3 substrate receptors...
  54. Wilkins A, Ping Q, Carpenter C. RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex. Genes Dev. 2004;18:856-61 pubmed
    ..In this report, we demonstrate that RhoBTB2 binds to the ubiquitin ligase scaffold, Cul3, via its first BTB domain and show in vitro and in vivo that RhoBTB2 is a substrate for a Cul3-based ubiquitin ..
  55. Tsuji S, Yamashita M, Unishi G, Takewa R, Kimata T, Isobe K, et al. A young child with pseudohypoaldosteronism type II by a mutation of Cullin 3. BMC Nephrol. 2013;14:166 pubmed publisher
    ..Here, we firstly report on the Japanese child of PHA II caused by a mutation of CUL 3.
  56. Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N, et al. Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene. 1999;18:6829-34 pubmed
    ..The enhanced expression of all Cul-family proteins except Cul-5 was observed in a variety of tumor cell lines. ..
  57. Wimuttisuk W, Singer J. The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer. Mol Biol Cell. 2007;18:899-909 pubmed
    ..Cullin3 (Cul3) forms a catalytically inactive BTB-Cul3-Rbx1 (BCR) ubiquitin ligase, which becomes functional upon covalent ..