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The human F box protein β-Trcp associates with the Cul1/Skp1 complex and regulates the stability of β-catenin


Ubiquitin-conjugation targets numerous cellular regulators for proteasome-mediated degradation. Thus, the identification of ubiquitin ligases and their physiological substrates is crucially important, especially for those cases in which aberrant levels of regulatory proteins (e.g., β-catenin, p27) result from a deregulated ubiquitination pathway. In yeast, the proteolysis of several G1 regulators is controlled by ubiquitin ligases (or SCFs) formed by three subunits: Skp1, Cul A (Cdc53), and one of many F-box proteins. Specific F-box proteins (Fbps) recruit different substrates to the SCF. Although many Fbps have been identified in mammals, their specific substrates and the existence of multiple SCFs have not yet been reported. We have found that one human Fbp, β-Trcp (β-Transducin repeat containing protein), does indeed form a novel SCF with human Skp1 and Cul1. Consistent with recent reports indicating that Xenopus and Drosophila β-Trcp homologs act as negative regulators of the Wnt/β-catenin signaling pathway, we report here that human β-Trcp interacts with β-catenin in vivo. Furthermore, β-catenin is specifically stabilized in vivo by the expression of a dominant negative β-Trcp. These results indicate that the Cul1/Skp1/β-Trcp complex forms a ubiquitin ligase that mediates the degradation of β-catenin.

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  • Bai C, Sen P, Hofman K, Ma L, Goebel M, Harper W and Elledge S. . 1996 Cell 86: 263–274.

  • Behrens J, von Kries J, Kuhl M, Bruhn L, Wedlich D, Grosschedl R and Birchmeier W. . 1996 Nature 382: 638–642.

  • Gonen H, Bercovich B, Orian A, Carrano AC, Whiteside S, Israël A, Pagano M, Iwai K and Ciechanover A. . (1999) submitted.

  • Hannon GJ. . 1995 In: Cell Cycle – Materials and Methods, Pagano M (ed.). Springer-Verlag, chapter 20: pp. 231–243.

    Google Scholar 

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da CL, Morin PJ, Vogelstein B and Kinzler KW. . 1998 Science 281: 1509–1512.

  • Jiang J and Struhl G. . 1998 Nature 391: 493–496.

  • Kipreos ET, Gohel SP and Hedgecock EM. . (1999) submitted.

  • Lisztwan J, Marti A, Sutterluty H, Gstaiger M, Wirbelauer C and Krek W. . 1998 EMBO J. 17: 368–383.

  • Lyapina SA, Correll CC, Kipreos ET and Deshaies RJ. . 1998 Proc. Natl. Acad. Sci. USA 95: 7451–7456.

  • Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V, Thomas D, Strebel K and Benarous R. . 1998 Molecular Cell 1: 565–574.

  • Marikawa Y and Elinson RP. . 1998 Mech. Dev. 77: 75–80.

  • Michel JJ and Xiong Y. . 1998 Cell Growth Differ. 9: 435–449.

  • Miller J and Moon R. . 1996 Genes and Devel. 10: 2527–2539.

  • Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destree O and Clevers H. . 1996 Cell 86: 391–399.

  • Mountain HA, Bystrom AS and Korch C. . 1993 Mol. Microbiol. 7: 215–228.

  • Pagano M. . 1997 FASEB J. 11: 1067–1075.

  • Pagano M, Pepperkok R, Lukas J, Baldin V, Ansorge W, Bartek J and Draetta G. . 1993 J. Cell Biol. 121: 101–111.

  • Pagano M, Tam S, Theodoras A, Beer P, Delsal G, Chau V, Yew R, Draetta G and Rolfe M. . 1995 Science 269: 682–685.

  • Pagano M, Theodoras AM, Tam SW and Draetta G. . 1994 Genes & Dev. 8: 1627–1639.

  • Peifer M. . 1997 Science 275: 1752–1753.

  • Pennisi E. . 1998 Science 281: 1438–1441.

  • Rubinfeld B, Souza B, Albert I, Muller O, Chamberlain S, Masiarz F, Munemitsu S and Polakis P. . 1993 Science 262: 1731–1734.

  • Skowyra D, Craig KL, Tyers M, Elledge SJ and Harper JW. . 1997 Cell 91: 209–219.

  • Spevak W, Keiper BD, Stratowa C and Castanon MJ. . 1993 Mol. Cell. Biol. 13: 4953–4966.

  • Su L, Vogelstein B and Kinzler K. . 1993 Science 262: 1734–1737.

  • Yu ZK, Gervais J and Zhang H. . 1998 Proc. Natl. Acad. Sci. USA 95: 11324–11329.

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We thank M Garabedian, E Kipreos, D Morgan, Y Xiong for reagents; J Bloom, AC Carrano, C Cenciarelli, S Guadagno (Zymed Inc.), A Hershko and MT Petrucci for their contribution to this work; and J Bloom and L Yamasaki for critically reading the manuscript. EL is supported by the Molecular Oncology Program (NIH 5T32-CA09161); MP is in part supported by a HFSPO grant RG0229/98-M and NIH grants RO1-CA76584 and RO1-GM57587.

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Latres, E., Chiaur, D. & Pagano, M. The human F box protein β-Trcp associates with the Cul1/Skp1 complex and regulates the stability of β-catenin. Oncogene 18, 849–854 (1999).

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