beta transducin repeat containing proteins

Summary

Summary: A family of F-box domain proteins that contain sequences that are homologous to the beta subunit of transducin (BETA-TRANSDUCIN). They play an important role in the protein degradation pathway by becoming components of SKP CULLIN F-BOX PROTEIN LIGASES, which selectively act on a subset of proteins including beta-catenin and IkappaBbeta.

Top Publications

  1. Belaïdouni N, Peuchmaur M, Perret C, Florentin A, Benarous R, Besnard Guerin C. Overexpression of human beta TrCP1 deleted of its F box induces tumorigenesis in transgenic mice. Oncogene. 2005;24:2271-6 pubmed
    ..These results show that the overexpression of Delta F beta TrCP1 or beta TrCP1 in vivo induce tumors through beta-catenin activation. ..
  2. Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, et al. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J. 1999;18:2401-10 pubmed
    ..SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability. ..
  3. Shirogane T, Jin J, Ang X, Harper J. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem. 2005;280:26863-72 pubmed
  4. 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
    ..Our results show that beta-TrCP has a crucial role in mediating the response to DNA damage through Cdc25A degradation. ..
  5. Lassot I, Segeral E, Berlioz Torrent C, Durand H, Groussin L, Hai T, et al. ATF4 degradation relies on a phosphorylation-dependent interaction with the SCF(betaTrCP) ubiquitin ligase. Mol Cell Biol. 2001;21:2192-202 pubmed
    ..ATF4 represents a novel substrate for the SCF(betaTrCP) complex, which is the first mammalian E3 ubiquitin ligase identified so far for the control of the degradation of a bZIP transcription factor. ..
  6. Ray D, Osmundson E, Kiyokawa H. Constitutive and UV-induced fibronectin degradation is a ubiquitination-dependent process controlled by beta-TrCP. J Biol Chem. 2006;281:23060-5 pubmed
    ..Taken together, constitutive FN degradation, as well as UV-induced degradation, is ubiquitination dependent and controlled by beta-TrCP. ..
  7. Butticaz C, Michielin O, Wyniger J, Telenti A, Rothenberger S. Silencing of both beta-TrCP1 and HOS (beta-TrCP2) is required to suppress human immunodeficiency virus type 1 Vpu-mediated CD4 down-modulation. J Virol. 2007;81:1502-5 pubmed
  8. Ougolkov A, Zhang B, Yamashita K, Bilim V, Mai M, Fuchs S, et al. Associations among beta-TrCP, an E3 ubiquitin ligase receptor, beta-catenin, and NF-kappaB in colorectal cancer. J Natl Cancer Inst. 2004;96:1161-70 pubmed
  9. Meusser B, Sommer T. Vpu-mediated degradation of CD4 reconstituted in yeast reveals mechanistic differences to cellular ER-associated protein degradation. Mol Cell. 2004;14:247-58 pubmed
    ..In contrast, the cellular ER-associated protein degradation pathway can transport ER-lumenal parts of CD4 into the cytoplasm before ubiquitination and extraction of the membrane anchor. ..

More Information

Publications62

  1. Evrard Todeschi N, Gharbi Benarous J, Bertho G, Coadou G, Megy S, Benarous R, et al. NMR studies for identifying phosphopeptide ligands of the HIV-1 protein Vpu binding to the F-box protein beta-TrCP. Peptides. 2006;27:194-210 pubmed
    ..These findings are in good agreement with a recently published X-ray structure of a shorter beta-Catenin fragment with the beta-TrCP complex. ..
  2. Nakayama K, Hatakeyama S, Maruyama S, Kikuchi A, Onoe K, Good R, et al. Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 gene. Proc Natl Acad Sci U S A. 2003;100:8752-7 pubmed
    ..In addition, they implicate beta-TrCP1 in the maintenance of ploidy during cell-cycle progression. ..
  3. Gerstein A, Almeida T, Zhao G, Chess E, Shih I, Buhler K, et al. APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer. 2002;34:9-16 pubmed
    ..These results suggest that CTNNB1 signaling plays a critical role in the development of a significant fraction of prostate cancers. Moreover, they provide the first evidence that hTRCP1 plays a role in human neoplasia. ..
  4. Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung M, et al. GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell. 2008;13:36-47 pubmed publisher
    ..Importantly, a strong correlation between Cdc25A overproduction and GSK-3beta inactivation was observed in human tumor tissues, indicating that GSK-3beta inactivation may account for Cdc25A overproduction in a subset of human tumors. ..
  5. Frescas D, Pagano M. Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer. 2008;8:438-49 pubmed publisher
  6. Westbrook T, Hu G, Ang X, Mulligan P, Pavlova N, Liang A, et al. SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature. 2008;452:370-4 pubmed publisher
    ..Thus, REST is a key target in beta-TRCP-driven transformation and the beta-TRCP-REST axis is a new regulatory pathway controlling neurogenesis. ..
  7. 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. ..
  8. Margottin F, Bour S, Durand H, Selig L, Benichou S, Richard V, et al. A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell. 1998;1:565-74 pubmed
    ..These data suggest that beta TrCP and Skp1p represent components of a novel ER-associated protein degradation pathway that mediates CD4 proteolysis. ..
  9. Ding Q, He X, Hsu J, Xia W, Chen C, Li L, et al. Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol. 2007;27:4006-17 pubmed
    ..Our results indicate that the turnover of Mcl-1 by beta-TrCP is an essential mechanism for GSK-3beta-induced apoptosis and contributes to GSK-3beta-mediated tumor suppression and chemosensitization. ..
  10. Mamely I, van Vugt M, Smits V, Semple J, Lemmens B, Perrakis A, et al. Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery. Curr Biol. 2006;16:1950-5 pubmed
    ..Moreover, our data demonstrate that the degradation of Claspin at the onset of mitosis is an essential step for the recovery of a cell from a DNA-damage-induced cell-cycle arrest. ..
  11. van Kerkhof P, Putters J, Strous G. The ubiquitin ligase SCF(betaTrCP) regulates the degradation of the growth hormone receptor. J Biol Chem. 2007;282:20475-83 pubmed
    ..Together, these findings provide direct evidence for a key role of the SCF(TrCP) in the endocytosis and degradation of an important factor in growth, immunity, and life span regulation. ..
  12. Liang C, Zhang M, Sun S. beta-TrCP binding and processing of NF-kappaB2/p100 involve its phosphorylation at serines 866 and 870. Cell Signal. 2006;18:1309-17 pubmed
    ..These data suggest that p100 processing involves its phosphorylation at specific terminal serines, which form a binding site for beta-TrCP thereby regulating p100 ubiquitination. ..
  13. Seo E, Kim H, Kim R, Yun S, Kim M, Han J, et al. Multiple isoforms of beta-TrCP display differential activities in the regulation of Wnt signaling. Cell Signal. 2009;21:43-51 pubmed publisher
    ..Overall, our data suggest that isoforms of beta-TrCPs generated by alternative splicing may have different biological roles. ..
  14. 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. ..
  15. Müerköster S, Arlt A, Sipos B, Witt M, Grossmann M, Kloppel G, et al. Increased expression of the E3-ubiquitin ligase receptor subunit betaTRCP1 relates to constitutive nuclear factor-kappaB activation and chemoresistance in pancreatic carcinoma cells. Cancer Res. 2005;65:1316-24 pubmed
    ..Altogether, our findings of the elevated betaTRCP1 expression in pancreatic carcinoma cells pinpoint to another important mediator of constitutive NF-kappaB activation and thereby of chemoresistance. ..
  16. Fuchs S, Spiegelman V, Kumar K. The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer. Oncogene. 2004;23:2028-36 pubmed
    ..Mechanisms underlying beta-TrCP regulation and their aberration in human and animal cancer as well as prospective of targeting beta-TrCP as a means of anticancer therapy are also discussed. ..
  17. Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta G. Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell Cycle. 2004;3:469-71 pubmed
    ..According to our model, phosphorylation at Ser 76 is a "priming" step required for Ser 82 phosphorylation, which in turn allows recruitment of Cdc25A by betaTrCP and subsequent betaTrCP-dependent degradation. ..
  18. 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
  19. Jin J, Ang X, Ye X, Livingstone M, Harper J. Differential roles for checkpoint kinases in DNA damage-dependent degradation of the Cdc25A protein phosphatase. J Biol Chem. 2008;283:19322-8 pubmed publisher
    ..These data support the idea that Chk1 is the primary signal transducer linking activation of the ATM/ATR kinases to Cdc25A destruction in response to ionizing radiation. ..
  20. Wu C, Ghosh S. beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta. J Biol Chem. 1999;274:29591-4 pubmed
    ..Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta. ..
  21. 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. ..
  22. Sadot E, Simcha I, Iwai K, Ciechanover A, Geiger B, Ben Ze ev A. Differential interaction of plakoglobin and beta-catenin with the ubiquitin-proteasome system. Oncogene. 2000;19:1992-2001 pubmed
  23. Kumar K, Barriere H, Carbone C, Liu J, Swaminathan G, Xu P, et al. Site-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosis. J Cell Biol. 2007;179:935-50 pubmed
  24. Mitchell R, Katsura C, Skasko M, Fitzpatrick K, Lau D, Ruiz A, et al. Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog. 2009;5:e1000450 pubmed publisher
    ..Together, the data support a model in which Vpu co-opts the beta-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor. ..
  25. Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M, et al. Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell. 2003;4:799-812 pubmed
    ..Thus, beta-Trcp1 regulates the timely order of meiotic and mitotic events. ..
  26. Dorrello N, Peschiaroli A, Guardavaccaro D, Colburn N, Sherman N, Pagano M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006;314:467-71 pubmed
    ..We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth. ..
  27. Kumar K, Tang W, Ravindranath A, Clark W, Croze E, Fuchs S. SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor. EMBO J. 2003;22:5480-90 pubmed
    ..These findings characterize SCF(HOS) as an E3 ubiquitin ligase that is essential for ubiquitination, proteolysis and down-regulation of IFNAR1, and implicate HOS in the regulation of cellular responses to IFNalpha. ..
  28. Watanabe N, Arai H, Iwasaki J, Shiina M, Ogata K, Hunter T, et al. Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. Proc Natl Acad Sci U S A. 2005;102:11663-8 pubmed
    ..Using a specific inhibitor of CK2, we showed that the phosphorylation-dependent degradation of Wee1A is important for the proper onset of mitosis. ..
  29. Ray D, Terao Y, Nimbalkar D, Chu L, Donzelli M, Tsutsui T, et al. Transforming growth factor beta facilitates beta-TrCP-mediated degradation of Cdc25A in a Smad3-dependent manner. Mol Cell Biol. 2005;25:3338-47 pubmed
    ..These data suggest that Smad3 plays a key role in the regulation of Cdc25A ubiquitination by SCFbeta-TrCP and that Cdc25A stabilization observed in various cancers could be associated with defects in the TGF-beta-Smad3 pathway. ..
  30. Besnard Guerin C, Belaïdouni N, Lassot I, Segeral E, Jobart A, Marchal C, et al. HIV-1 Vpu sequesters beta-transducin repeat-containing protein (betaTrCP) in the cytoplasm and provokes the accumulation of beta-catenin and other SCFbetaTrCP substrates. J Biol Chem. 2004;279:788-95 pubmed
    ..These data suggest that Vpu is a strong competitive inhibitor of betaTrCP that impairs the degradation of SCFbetaTrCP substrates as long as Vpu has an intact phosphorylation motif and can bind to betaTrCP. ..
  31. Koch A, Waha A, Hartmann W, Hrychyk A, Schüller U, Waha A, et al. Elevated expression of Wnt antagonists is a common event in hepatoblastomas. Clin Cancer Res. 2005;11:4295-304 pubmed
    ..We propose that Nkd-1 and beta-TrCP may be used as possible diagnostic markers for the activated Wnt signaling pathway in hepatoblastomas. ..
  32. Margottin Goguet F, Hsu J, Loktev A, Hsieh H, Reimann J, Jackson P. Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev Cell. 2003;4:813-26 pubmed
    ..We hypothesize that Emi1 destruction relieves a late prophase checkpoint for APC activation. ..
  33. Kanemori Y, Uto K, Sagata N. Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. Proc Natl Acad Sci U S A. 2005;102:6279-84 pubmed
  34. Nakayama K, Nakayama K. Regulation of the cell cycle by SCF-type ubiquitin ligases. Semin Cell Dev Biol. 2005;16:323-33 pubmed
    ..Clinical evidence also suggests that dysregulation of these F-box proteins contributes to human cancers. ..
  35. Estrabaud E, Lassot I, Blot G, Le Rouzic E, Tanchou V, Quemeneur E, et al. RASSF1C, an isoform of the tumor suppressor RASSF1A, promotes the accumulation of beta-catenin by interacting with betaTrCP. Cancer Res. 2007;67:1054-61 pubmed
    ..Thus, RASSF1A and RASSF1C have opposite effects on beta-catenin degradation. Our results suggest that RASSF1C expression in the absence of RASSF1A could play a role in tumorigenesis. ..
  36. Bour S, Perrin C, Akari H, Strebel K. The human immunodeficiency virus type 1 Vpu protein inhibits NF-kappa B activation by interfering with beta TrCP-mediated degradation of Ikappa B. J Biol Chem. 2001;276:15920-8 pubmed
    ..However, in the presence of Vpu, this HIV-mediated NF-kappaB activation was markedly reduced. These results suggest that Vpu modulates both virus- and cytokine-induced activation of NF-kappaB in HIV-1-infected cells. ..
  37. Tang W, Li Y, Yu D, Thomas Tikhonenko A, Spiegelman V, Fuchs S. Targeting beta-transducin repeat-containing protein E3 ubiquitin ligase augments the effects of antitumor drugs on breast cancer cells. Cancer Res. 2005;65:1904-8 pubmed
    ..These data provide the proof of principle that targeting beta-TrCP might be beneficial for anticancer therapies. ..
  38. Douglas J, Viswanathan K, McCarroll M, Gustin J, Fruh K, Moses A. Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism. J Virol. 2009;83:7931-47 pubmed publisher
    ..Understanding the molecular mechanisms of both Vpu-dependent and -independent mediated antagonism of BST-2 will be critical for therapeutic strategies that exploit this novel viral function. ..
  39. Hsu K, Seharaseyon J, Dong P, Bour S, Marban E. Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol Cell. 2004;14:259-67 pubmed
    ..This virus-host interaction may influence HIV-1/AIDS progression, as well as electrical signaling in infected host tissues. ..
  40. Kudo Y, Guardavaccaro D, Santamaria P, Koyama Nasu R, Latres E, Bronson R, et al. Role of F-box protein betaTrcp1 in mammary gland development and tumorigenesis. Mol Cell Biol. 2004;24:8184-94 pubmed
  41. Melixetian M, Klein D, Sørensen C, Helin K. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat Cell Biol. 2009;11:1247-53 pubmed publisher
    ..Taken together, these results demonstrate that NEK11 is an important component of the pathway enforcing the G2/M checkpoint, suggesting that genetic mutations in NEK11 may contribute to the development of human cancer. ..
  42. Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning A, et al. Identification of the receptor component of the IkappaBalpha-ubiquitin ligase. Nature. 1998;396:590-4 pubmed
    ..When these receptor components recognize their specific ligand, which is a conserved, phosphorylation-based sequence motif, they target regulatory proteins containing this motif for proteasomal degradation. ..
  43. Xia Y, Padre R, de Mendoza T, Bottero V, Tergaonkar V, Verma I. Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci U S A. 2009;106:2629-34 pubmed publisher
    ..Our results identify IKK2 and beta-TrCP1 as novel regulators of the p53 pathway and suggest that blocking of IKK2 and beta-TrCP1 could be a means of regulating p53 stability and thereby modulating its biological activity. ..
  44. Davis M, Hatzubai A, Andersen J, Ben Shushan E, Fisher G, Yaron A, et al. Pseudosubstrate regulation of the SCF(beta-TrCP) ubiquitin ligase by hnRNP-U. Genes Dev. 2002;16:439-51 pubmed
    ..Our study points to a novel regulatory mechanism, which secures the localization, stability, substrate binding threshold, and efficacy of a specific protein-ubiquitin ligase. ..
  45. Chen W, Lee J, Cho S, Fine H. Proteasome-mediated destruction of the cyclin a/cyclin-dependent kinase 2 complex suppresses tumor cell growth in vitro and in vivo. Cancer Res. 2004;64:3949-57 pubmed
    ..These data demonstrate that cyclin A and/or the cyclin A/cdk2 complex is a promising anticancer target with a high therapeutic index. ..
  46. Isoda M, Kanemori Y, Nakajo N, Uchida S, Yamashita K, Ueno H, et al. The extracellular signal-regulated kinase-mitogen-activated protein kinase pathway phosphorylates and targets Cdc25A for SCF beta-TrCP-dependent degradation for cell cycle arrest. Mol Biol Cell. 2009;20:2186-95 pubmed publisher
    ..These results suggest that strong ERK activation can target Cdc25A for degradation in a manner similar to, but independent of, Chk1 for cell cycle arrest. ..
  47. Peschiaroli A, Skaar J, Pagano M, Melino G. The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene. 2010;29:1384-93 pubmed publisher
    ..In conclusion, we showed that USP47, a novel beta-Trcp interactor, regulates cell growth and survival, potentially providing a novel target for anticancer therapies. ..
  48. Tsai W, Chung Y, Zou Y, Park S, Xu Z, Nakayama K, et al. Inhibition of FOXO3 tumor suppressor function by betaTrCP1 through ubiquitin-mediated degradation in a tumor mouse model. PLoS ONE. 2010;5:e11171 pubmed publisher
    ..These findings significantly contribute to understanding of the control of FOXO3 stability in cancer cells and may provide opportunities for developing innovative anticancer therapeutic modalities. ..
  49. Plotnikov A, Li Y, Tran T, Tang W, Palazzo J, Rui H, et al. Oncogene-mediated inhibition of glycogen synthase kinase 3 beta impairs degradation of prolactin receptor. Cancer Res. 2008;68:1354-61 pubmed publisher
  50. O Connor S, Markovina S, Miyamoto S. Evidence for a phosphorylation-independent role for Ser 32 and 36 in proteasome inhibitor-resistant (PIR) IkappaBalpha degradation in B cells. Exp Cell Res. 2005;307:15-25 pubmed
    ..These results suggest that B lineage cells can differentiate between PIR and canonical IkappaBalpha degradation through the absence or presence of dually phosphorylated IkappaBalpha. ..
  51. Mo Z, Zu X, Xie Z, Li W, Ning H, Jiang Y, et al. Antitumor effect of F-PBF(beta-TrCP)-induced targeted PTTG1 degradation in HeLa cells. J Biotechnol. 2009;139:6-11 pubmed publisher
    ..In conclusion, targeted degradation of PTTG1 by F-PBF(beta-TrCP) has antitumor activity in vitro in HeLa cells. These results suggest that F-PBF(beta-TrCP) could be used for cancer treatment by targeted degradation of PTTG1. ..
  52. Strack P, Caligiuri M, Pelletier M, Boisclair M, Theodoras A, Beer Romero P, et al. SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4. Oncogene. 2000;19:3529-36 pubmed
    ..Our results also suggest that ubiquitin is transferred directly from the Ubc to phospho-I kappa B alpha in a SCF beta-TRCP dependent reaction. Oncogene (2000) 19, 3529 - 3536 ..
  53. Vuillard L, Nicholson J, Hay R. A complex containing betaTrCP recruits Cdc34 to catalyse ubiquitination of IkappaBalpha. FEBS Lett. 1999;455:311-4 pubmed
    ..In the presence of ubiquitin activating enzyme and the protein complex containing betaTrCP, polyubiquitination of IkappaBalpha peptide was dependent on the presence of Cdc34, while Ubc5 only stimulated mono- and di-ubiquitination. ..