Gene Symbol: BTRC
Description: beta-transducin repeat containing E3 ubiquitin protein ligase
Alias: BETA-TRCP, FBW1A, FBXW1, FBXW1A, FWD1, bTrCP, bTrCP1, betaTrCP, F-box/WD repeat-containing protein 1A, E3RSIkappaB, F-box and WD repeats protein beta-TrCP, F-box and WD-repeat protein 1B, beta-TrCP1, epididymis tissue protein Li 2a, pIkappaBalpha-E3 receptor subunit
Species: human
Products:     BTRC

Top Publications

  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. 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 act as an adapter linking CD4 with the ubiquitin-proteasome machinery via interaction with the F-box protein betaTrCP. To identify additional cellular betaTrCP-dependent Vpu targets, we performed quantitative proteomics analyses ..
  3. 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
    ..These results indicate that the Cul1/Skp1/beta-Trcp complex forms a ubiquitin ligase that mediates the degradation of beta-catenin. ..
  4. Tan M, Gallegos J, Gu Q, Huang Y, Li J, Jin Y, et al. SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia. 2006;8:1042-54 pubmed
    ..Thus, pro-caspase-3 appears to be a substrate of SAG/ROC-SCF(beta-TrCP) E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3. ..
  5. Putters J, Slotman J, Gerlach J, Strous G. Specificity, location and function of ?TrCP isoforms and their splice variants. Cell Signal. 2011;23:641-7 pubmed publisher
    ..Interestingly, we find that one splice variant of ?TrCP2 localises exclusively to the nucleus and another only to the cytosol. In addition, we show that the substrate binding domain of ?TrCP is the dominant localisation determinant. ..
  6. Mailand N, Bekker Jensen S, Bartek J, Lukas J. Destruction of Claspin by SCFbetaTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress. Mol Cell. 2006;23:307-18 pubmed
    ..interaction was phosphorylation dependent and required the activity of the Plk1 kinase and the integrity of a betaTrCP recognition motif (phosphodegron) in the N terminus of Claspin...
  7. Lee Y, Kim E, Lee J, Jeoung D, Bae S, Kwon S, et al. HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential for mitotic progression. Cancer Res. 2008;68:7550-60 pubmed publisher
    ..From these findings, it was shown that Plk1 phosphorylates HSF1 in early mitosis and that the binding of phosphorylated HSF1 with Cdc20 and ubiquitin degradation by SCF(beta-TrCP) regulates mitotic progression. ..
  8. Maniatis T. A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev. 1999;13:505-10 pubmed
  9. Fong A, Sun S. Genetic evidence for the essential role of beta-transducin repeat-containing protein in the inducible processing of NF-kappa B2/p100. J Biol Chem. 2002;277:22111-4 pubmed
    ..Interestingly the constitutive processing of p100 mutants was independent of beta-TrCP. These results suggest that beta-TrCP is an essential component of NIK-induced p100 processing. ..

More Information


  1. 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. ..
  2. Bhatia N, Thiyagarajan S, Elcheva I, Saleem M, Dlugosz A, Mukhtar H, et al. Gli2 is targeted for ubiquitination and degradation by beta-TrCP ubiquitin ligase. J Biol Chem. 2006;281:19320-6 pubmed
    ..These data identify beta-TrCP2 as a pivotal regulator of Gli2 expression and point to an important role for posttranslational modulation of GLI2 protein levels in Hh pathway-associated human prostate cancer. ..
  3. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci U S A. 2004;101:4419-24 pubmed
    ..These results also establish the existence of a feedback loop between Cdc2 and Wee1A in somatic cells that depends on ubiquitination and protein degradation and ensures the rapid activation of Cdc2 when cells are ready to divide. ..
  4. Kee Y, Kim J, D Andrea A, D ANDREA A. Regulated degradation of FANCM in the Fanconi anemia pathway during mitosis. Genes Dev. 2009;23:555-60 pubmed publisher
    ..Nondegradable mutant forms of FANCM retain the FA core complex in the chromatin and disrupt the FA pathway. Our data provide a novel mechanism for the cell cycle-dependent regulation of the FA pathway. ..
  5. 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. ..
  6. 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. ..
  7. Malim M, Emerman M. HIV-1 accessory proteins--ensuring viral survival in a hostile environment. Cell Host Microbe. 2008;3:388-98 pubmed publisher
    ..Broadly speaking, the HIV-1 accessory proteins modify the local environment within infected cells to ensure viral persistence, replication, dissemination, and transmission. ..
  8. 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. ..
  9. 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
    ..rapidly phosphorylated on Ser67 by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase SCF(betaTRCP)...
  10. Hill M, Ruiz A, Schmitt K, Stephens E. Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Virology. 2010;397:104-12 pubmed publisher
    ..Taken together, these results indicate that amino acid substitutions in the second alpha-helical domain that retain the predicted structure and binding to h-beta-TrCP1 can influence Vpu-mediated CD4 degradation. ..
  11. Wei S, Chuang H, Tsai W, Yang H, Ho S, Paterson A, et al. Thiazolidinediones mimic glucose starvation in facilitating Sp1 degradation through the up-regulation of beta-transducin repeat-containing protein. Mol Pharmacol. 2009;76:47-57 pubmed publisher
    ..The ability of OSU-CG12 to mimic glucose starvation to activate beta-TrCP-mediated Sp1 degradation has translational potential to foster novel strategies for cancer therapy. ..
  12. 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. ..
  13. 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
  14. 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
  15. Furukawa M, Zhang Y, McCarville J, Ohta T, Xiong Y. The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1. Mol Cell Biol. 2000;20:8185-97 pubmed
    ..This pathway may be commonly utilized for the assembly of other cullin ligases. ..
  16. 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
  17. Gluschnaider U, Hidas G, Cojocaru G, Yutkin V, Ben Neriah Y, Pikarsky E. beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor. PLoS ONE. 2010;5:e9060 pubmed publisher
    ..Together these observations suggest that AhR activation may be a cancer counteracting mechanism in the prostate. We maintain that combining beta-TrCP inhibition with androgen ablation could benefit advanced prostate cancer patients. ..
  18. Gao Z, Seeling J, Hill V, Yochum A, Virshup D. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc Natl Acad Sci U S A. 2002;99:1182-7 pubmed
    ..The data suggest that CKI phosphorylates and destabilizes the beta-catenin degradation complex, likely through the dissociation of PP2A, providing a mechanism by which CKI stabilizes beta-catenin and propagates the Wnt signal. ..
  19. Li Y, Clevenger C, Minkovsky N, Kumar K, Raghunath P, Tomaszewski J, et al. Stabilization of prolactin receptor in breast cancer cells. Oncogene. 2006;25:1896-902 pubmed
    ..These findings represent a novel mechanism through which altered PRLr stability may directly influence the pathogenesis of breast cancer. ..
  20. Saha A, Deshaies R. Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation. Mol Cell. 2008;32:21-31 pubmed publisher
  21. Wei S, Yang H, Chuang H, Yang J, Kulp S, Lu P, et al. A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells. J Biol Chem. 2008;283:26759-70 pubmed publisher
    ..Moreover, we obtained evidence that this beta-TrCP-dependent degradation takes part in controlling cyclin D1 turnover when cancer cells undergo glucose starvation, which endows physiological relevance to this novel mechanism. ..
  22. Binette J, Dubé M, Mercier J, Halawani D, Latterich M, Cohen E. Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum. Retrovirology. 2007;4:75 pubmed
  23. 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
  24. Meyer L, Deau B, Forejtnikovà H, Dumenil D, Margottin Goguet F, Lacombe C, et al. beta-Trcp mediates ubiquitination and degradation of the erythropoietin receptor and controls cell proliferation. Blood. 2007;109:5215-22 pubmed
  25. 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
  26. Zhao Y, Xiong X, Sun Y. DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(?TrCP) E3 ubiquitin ligase and regulates survival and autophagy. Mol Cell. 2011;44:304-16 pubmed publisher
    ..Furthermore, DEPTOR accumulates upon glucose deprivation and mTOR inhibition to induce autophagy. Thus, ?TrCP-DEPTOR-mTOR intertwine to regulate cell survival and autophagy. ..
  27. Li V, Ng S, Boersema P, Low T, Karthaus W, Gerlach J, et al. Wnt signaling through inhibition of ?-catenin degradation in an intact Axin1 complex. Cell. 2012;149:1245-56 pubmed publisher
    ..Subsequently, newly synthesized ?-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors. ..
  28. Hart M, Concordet J, Lassot I, Albert I, del los Santos R, Durand H, et al. The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol. 1999;9:207-10 pubmed
    ..In contrast, beta-TrCP2 did not associate with beta-catenin. We conclude that beta-TrCP is a component of an E3 ubiquitin ligase that is responsible for the targeted degradation of phosphorylated beta-catenin. ..
  29. Sauter D, Unterweger D, Vogl M, Usmani S, Heigele A, Kluge S, et al. Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein. PLoS Pathog. 2012;8:e1003093 pubmed publisher
    ..These results indicate that HIV-1 group N Vpu is under strong host-specific selection pressure and that the acquisition of effective tetherin antagonism may lead to the emergence of viral variants with increased transmission fitness. ..
  30. 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. ..
  31. 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. ..
  32. 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 suggest that by restricting SKP1-CUL1 interaction, CAND1 regulated the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes. ..
  33. 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
    ..Here we show that the F-box protein betaTrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for IkappaBalpha and beta-catenin degradation, ..
  34. 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
    ..Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary ..
  35. Tervo H, Homann S, Ambiel I, Fritz J, Fackler O, Keppler O. ?-TrCP is dispensable for Vpu's ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 release. Retrovirology. 2011;8:9 pubmed publisher
    ..Moreover, we propose the existence of a critical, yet to be identified cellular factor that interacts with Vpu via its di-serine motif to alter the trafficking of the restriction factor. ..
  36. 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. ..
  37. 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
    ..This component, which we denote E3RSIkappaB (pIkappaBalpha-E3 receptor subunit), binds specifically to pIkappaBalpha and promotes its in vitro ..
  38. 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. ..
  39. Schmid T, Jansen A, Baker A, Hegamyer G, Hagan J, Colburn N. Translation inhibitor Pdcd4 is targeted for degradation during tumor promotion. Cancer Res. 2008;68:1254-60 pubmed publisher
    ..Thus, because endogenous Pdcd4 levels are limiting for tumorigenesis, inhibiting signaling to Pdcd4 degradation may prove a valid strategy for cancer prevention and intervention. ..
  40. Tsuchiya Y, Morita T, Kim M, Iemura S, Natsume T, Yamamoto M, et al. Dual regulation of the transcriptional activity of Nrf1 by ?-TrCP- and Hrd1-dependent degradation mechanisms. Mol Cell Biol. 2011;31:4500-12 pubmed publisher
    ..Thus, these results clearly suggest that both ?-TrCP- and Hrd1-dependent degradation mechanisms regulate the transcriptional activity of Nrf1 to maintain cellular homeostasis. ..
  41. Chan E, Santamaria A, Sillje H, Nigg E. Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora. Chromosoma. 2008;117:457-69 pubmed publisher
    ..This suggests that Plk1 controls Aurora A localization and function by regulating cellular levels of hBora. ..
  42. Tempé D, Casas M, Karaz S, Blanchet Tournier M, Concordet J. Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP. Mol Cell Biol. 2006;26:4316-26 pubmed
    ..We identified multiple betaTrCP-binding sites related to the DSGX2-4S motif in Gli3, which are intertwined with PKA and GSK3beta sites, and ..
  43. 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. ..
  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. 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
    ..This process involves the recruitment of human betaTrCP (TrCP), a key member of the SkpI-Cdc53-F-box E3 ubiquitin ligase complex that specifically interacts with ..
  46. Jin J, Ang X, Shirogane T, Wade Harper J. Identification of substrates for F-box proteins. Methods Enzymol. 2005;399:287-309 pubmed
    ..In addition, we describe approaches for the use of immobilized phosphopeptides to identify F-box proteins that recognize particular phosphodegrons. ..
  47. Duan S, Skaar J, Kuchay S, Toschi A, Kanarek N, Ben Neriah Y, et al. mTOR generates an auto-amplification loop by triggering the ?TrCP- and CK1?-dependent degradation of DEPTOR. Mol Cell. 2011;44:317-24 pubmed publisher
    ..Moreover, our results suggest that pharmacologic inhibition of CK1 may be a viable therapeutic option for the treatment of cancers characterized by activation of mTOR-signaling pathways. ..
  48. 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. ..
  49. Limón Mortés M, Mora Santos M, Espina A, Pintor Toro J, López Román A, Tortolero M, et al. UV-induced degradation of securin is mediated by SKP1-CUL1-beta TrCP E3 ubiquitin ligase. J Cell Sci. 2008;121:1825-31 pubmed publisher
    ..Moreover, we show that GSK-3beta inhibitors prevent securin degradation, and that CUL1 and betaTrCP are involved in this depletion...
  50. Hattori K, Hatakeyama S, Shirane M, Matsumoto M, Nakayama K. Molecular dissection of the interactions among IkappaBalpha, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of IkappaBalpha. J Biol Chem. 1999;274:29641-7 pubmed
    The SCF complex containing Skp1, Cul1, and the F-box protein FWD1 (the mouse homologue of Drosophila Slimb and Xenopus beta-TrCP) functions as the ubiquitin ligase for IkappaBalpha...
  51. 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
    ..Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta ..
  52. Villalobos V, Naik S, Bruinsma M, Dothager R, Pan M, Samrakandi M, et al. Dual-color click beetle luciferase heteroprotein fragment complementation assays. Chem Biol. 2010;17:1018-29 pubmed publisher
    ..These dual-color protein interaction switches may enable directed dynamic analysis of a variety of protein interactions in living cells. ..
  53. Spiegelman V, Tang W, Chan A, Igarashi M, Aaronson S, Sassoon D, et al. Induction of homologue of Slimb ubiquitin ligase receptor by mitogen signaling. J Biol Chem. 2002;277:36624-30 pubmed
    ..These data link the induction of HOS in proliferating cells with mitogen-signaling-dependent inhibition of cell differentiation and promotion of cell transformation. ..
  54. 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. ..
  55. 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
    ..Thus, in multiple myeloma, Fbxw7? and GSK3 function as pro-survival factors through the control of p100 degradation. ..
  56. Meyer R, Srinivasan S, Singh A, Mahoney J, Gharahassanlou K, Rahimi N. PEST motif serine and tyrosine phosphorylation controls vascular endothelial growth factor receptor 2 stability and downregulation. Mol Cell Biol. 2011;31:2010-25 pubmed publisher
    ..The PEST domain acts as a dual modulator of VEGFR-2; the phosphorylation of S1188/S1191 controls ubiquitination and degradation via ?-Trcp1, where the phosphorylation of Y1173 through PKA/p38 MAPK controls the stability of VEGFR-2. ..
  57. Ohta T, Xiong Y. Phosphorylation- and Skp1-independent in vitro ubiquitination of E2F1 by multiple ROC-cullin ligases. Cancer Res. 2001;61:1347-53 pubmed
    ..These results suggest a novel, SKP1-independent mechanism for targeting E2F1 ubiquitination. ..
  58. Spencer E, Jiang J, Chen Z. Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP. Genes Dev. 1999;13:284-94 pubmed
    ..These biochemical and genetic data strongly suggest that Slimb/beta-TrCP is the specificity determinant for the signal-induced ubiquitination of IkappaBalpha. ..
  59. Zhao B, Li L, Tumaneng K, Wang C, Guan K. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes Dev. 2010;24:72-85 pubmed publisher
  60. 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. ..
  61. 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
    ..In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCF(betaTrCP) ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases ..
  62. Su Y, Fu C, Ishikawa S, Stella A, Kojima M, Shitoh K, et al. APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase. Mol Cell. 2008;32:652-61 pubmed publisher
    ..Thus, by acting to protect the E3 ligase binding site, APC ensures the ubiquitin conjugation of phosphorylated beta-catenin. ..
  63. 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. ..
  64. 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
  65. Zheng H, Qian J, Varghese B, Baker D, FUCHS S. Ligand-stimulated downregulation of the alpha interferon receptor: role of protein kinase D2. Mol Cell Biol. 2011;31:710-20 pubmed publisher
    ..The mechanisms of the ligand-inducible elimination of IFNAR1 are discussed, along with the potential medical significance of this regulation. ..
  66. 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
    ..Here, we show that RASSF1C, but not RASSF1A, interacts with betaTrCP. Binding of RASSF1C to betaTrCP involves serine 18 and serine 19 of the SS(18)GYXS(19) motif present in RASSF1C ..
  67. 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. ..
  68. 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
  69. Peschiaroli A, Dorrello N, Guardavaccaro D, Venere M, Halazonetis T, Sherman N, et al. SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response. Mol Cell. 2006;23:319-29 pubmed
    ..We found that during recovery from the DNA replication checkpoint response, Claspin is degraded in a betaTrCP-dependent manner...
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    ..These results provide a new biomarker that may aid a rational use of tyrosine kinase inhibitors to treat refractory PTC. ..
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    ..Thus, our results point to a conformational control of CRL activity, with ligation of NEDD8 shifting equilibria to disfavor inactive CAND1-bound closed architectures, and favor dynamic, open forms that promote polyubiquitination. ..
  72. 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
    ..the synthesis of unphosphorylated beta-catenin that escapes recognition by the beta transducin repeat protein (beta TrCP1), the receptor of an ubiquitin...
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    ..Furthermore, inhibition of GSK-3beta results in the upregulation of Snail and downregulation of E-cadherin in vivo. Thus, Snail and GSK-3beta together function as a molecular switch for many signalling pathways that lead to EMT. ..
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    ..We suggest that catalyzed protein exchange may be a general feature of dynamic macromolecular machines and propose a hypothesis for how substrates, Nedd8, and Cand1 collaborate to regulate the cellular repertoire of SCF complexes. ..
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    ..The SCF(betaTrcp) (Skp1-Cullin1-F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells ..
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    ..This process requires the recruitment of human betaTrCP, a component of the Skp1-Cullin-F box (SCF) ubiquitin ligase complex, that interacts with phosphorylated Vpu ..
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    ..These findings highlight the exploitation of several TMD-mediated mechanisms by HIV-1 Vpu in order to downregulate CD4 and thus promote viral pathogenesis. ..
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    ..Such pool of I?B? may play an important role in the control of basal and signal-mediated NF-?B activity. ..
  80. 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. ..
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    ..that regulation of Cdc25A protein abundance during S phase and in response to DNA damage is mediated by SCF(betaTrCP) activity...
  82. 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. ..
  83. Mangeat B, Gers Huber G, Lehmann M, Zufferey M, Luban J, Piguet V. HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog. 2009;5:e1000574 pubmed publisher
    ..Identification of tetherin binding to Vpu provides a potential novel target for the development of drugs aimed at inhibiting HIV-1 replication. ..