Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Differential interaction of plakoglobin and β-catenin with the ubiquitin-proteasome system

Oncogene volume 19, pages 1992–2001 (2000)Cite this article

Abstract

β-Catenin and plakoglobin are closely related armadillo family proteins with shared and distinct properties; Both are associated with cadherins in actin-containing adherens junctions. Plakoglobin is also found in desmosomes where it anchors intermediate filaments to the desmosomal plaques. β-Catenin, on the other hand, is a component of the Wnt signaling pathway, which is involved in embryonic morphogenesis and tumorigenesis. A key step in the regulation of this pathway involves modulation of β-catenin stability. A multiprotein complex, regulated by Wnt, directs the phosphorylation of β-catenin and its degradation by the ubiquitin-proteasome system. Plakoglobin can also associate with members of this complex, but inhibition of proteasomal degradation has little effect on its levels while dramatically increasing the levels of β-catenin. β-TrCP, an F-box protein of the SCF E3 ubiquitin ligase complex, was recently shown to play a role in the turnover of β-catenin. To elucidate the basis for the apparent differences in the turnover of β-catenin and plakoglobin we compared the handling of these two proteins by the ubiquitin-proteasome system. We show here that a deletion mutant of β-TrCP, lacking the F-box, can stabilize the endogenous β-catenin leading to its nuclear translocation and induction of β-catenin/LEF-1-directed transcription, without affecting the levels of plakoglobin. However, when plakoglobin was overexpressed, it readily associated with β-TrCP, efficiently competed with β-catenin for binding to β-TrCP and became polyubiquitinated. Fractionation studies revealed that about 85% of plakoglobin in 293 cells, is Triton X-100-insoluble compared to 50% of β-catenin. These results suggest that while both plakoglobin and β-catenin can comparably interact with β-TrCP and the ubiquitination system, the sequestration of plakoglobin by the membrane-cytoskeleton system renders it inaccessible to the proteolytic machinery and stabilizes it.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Aberle H, Bierkamp C, Torchard D, Serova O, Wagner T, Natt E, Wirsching J, Heidkamper C, Montagna M and Lynch H . 1995 Proc Natl Acad Sci USA 92: 6384–6388

  • Aberle H, Bauer J, Stappert A, Kispert A and Kemler R . 1997 EMBO J 16: 3797–3804

  • Adams C and Nelson W . 1998 Curr Opin Cell Biol 10: 572–577

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

  • Behrens J, Jerchow B, Wurtele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D and Birchmeier W . 1998 Science 280: 596–599

  • Ben-Ze'ev A and Geiger B . 1998 Curr Opin Cell Biol 10: 629–639

  • Bierkamp C, Mclaughlin KJ, Schwarz H, Huber O and Kemler R . 1996 Dev Biol 180: 780–785

  • Chan E, Gat U, McNiff J and Fuchs E . 1999 Nat Genet 21: 410–413

  • Ciechanover A . 1998 EMBO J 17: 7151–7160

  • Cook D, Fry M, Hughes K, Sumathipala R, Woodgett J and Dale T . 1996 EMBO J 15: 4526–4536

  • Cowin P, Kapprell HP, Franke WW, Tamkun J and Hynes R . 1986 Cell 46: 1063–1073

  • Crawford H, Fingleton B, Rudolph-Owen L, Goss K, Rubinfeld B, Polakis P and Matrisian L . 1999 Oncogene 18: 2883–2891

  • de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A and Perret C . 1998 Proc Natl Acad Sci USA 95: 8847–8851

  • Eger A, Stockinger A, Schaffhauser B, Beug H and Foisner R . 2000 J Cell Biol 148: 173–187

  • Elledge SJ and Harper JW . 1998 Biochim Biophys Acta 1377: M61–70

  • Fagotto F, Funayama N, Gluck U and Gumbiner B . 1996 J Cell Biol 132: 1105–1114

  • Franke W, Goldschmidt MD, Zimbelmann R, Mueller HM, Schiller DL and Cowin P . 1989 Proc Natl Acad Sci USA 86: 4027–4031

  • Fuchs SY, Chen A, Xiong Y, Pan ZQ and Ronai Z . 1999 Oncogene 18: 2039–2046

  • Geiger B and Ayalon O . 1992 Annu Rev Cell Biol 8: 307–332

  • Haegel H, Larue L, Ohsugi M, Fedorov L, Herrenknecht K and Kemler R . 1995 Development 121: 3529–3537

  • Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R and Polakis P . 1999 Curr Biol 9: 207–210

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

  • Heasman J, Crawford A, Goldstone K, Garner-Hamrick P, Gumbiner B, McCrea P, Kintner C, Noro CY and Wylie C . 1994 Cell 79: 791–803

  • Hecht A, Litterst CM, Huber O and Kemler R . 1999 J Biol Chem 274: 18017–18025

  • Hershko A and Ciechanover A . 1998 Annu Rev Biochem 67: 425–479

  • Higuchi R, Krummel B and Saiki RK . 1988 Nucleic Acids Res 16: 7351–7367

  • Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG and Kemler R . 1996 Mech Dev 59: 3–10

  • Hulsken J, Birchmeier W and Behrens J . 1994 J Cell Biol 127: 2061–2069

  • Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S and Kikuchi A . 1998 EMBO J 17: 1371–1384

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

  • Kam Z, Jones MO, Chen H, Agad DA and Sedat JW . 1993 Bioimaging 1: 71–81

  • Karnovsky A and Klymkowsky MW . 1995 Proc Natl Acad Sci USA 92: 4522–4526

  • Kemler R . 1993 Trends Genet 9: 317–321

  • Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, Nakamichi I, Kikuchi A, Nakayama K and Nakayama K . 1999 EMBO J 18: 2401–2410

  • Klymkowsky M, Williams B, Barish G, Varmus H and Vourgourakis Y . 1999 Mol Cell Biol 10: 3151–3169

  • Kodama S, Ikeda S, Asahara T, Kishida M and Kikuchi A . 1999 J Biol Chem 274: 27682–27688

  • Kofron M, Spagnuolo A, Klymkowsky M, Wylie C and Heasman J . 1997 Development 124: 1553–1560

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B and Clevers H . 1997 Science 275: 1784–1787

  • Kowalczyk AP, Palka HL, Luu HH, Nilles LA, Anderson JE, Wheelock MJ and Green KJ . 1994 J Biol Chem 269: 31214–31223

  • Latres E, Chiaur DS and Pagano M . 1999 Oncogene 18: 849–854

  • Levenberg S, Yarden A, Kam Z and Geiger B . 1998 Oncogene 18: 869–876

  • Liu C, Kato Y, Zhang Z, Do VM, Yankner BA and He X . 1999 Proc Natl Acad Sci USA 96: 6273–6278

  • Maniatis T . 1999 Genes Dev 13: 505–510

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

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

  • Miller J and Moon RT . 1997 J Cell Biol 139: 229–243

  • Miyoshi Y, Iwao K, Nawa G, Yoshikawa H, Ochi T and Nakamura Y . 1998 Oncol Res 10: 591–594

  • 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

  • Morin P, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW . 1997 Science 275: 1787–1790

  • Munemitsu S, Albert I, Souza B, Rubinfeld B and Polakis P . 1995 Proc Natl Acad Sci USA 92: 3046–3050

  • Navarro P, Lozano E and Cano A . 1993 J Cell Sci 105: 923–934

  • Niwa H, Yamamura K and Miyazaki J . 1991 Gene 108: 193–199

  • Orford K, Crockett C, Jensen J, Weissman A and Byers S . 1997 J Biol Chem 272: 24735–24738

  • Ozawa M, Baribault H and Kemler R . 1989 EMBO J 8: 1711–1717

  • Palacios J and Gamallo C . 1998 Cancer Res 58: 1344–1347

  • Papkoff J, Rubinfeld B, Schryver B and Polakis P . 1996 Mol Cell Biol 16: 2128–21234

  • Patton EE, Willems AR, Sa D, Kuras L, Thomas D, Craig KL and Tyers M . 1998 Genes Dev 12: 692–705

  • Peifer M and Wieschaus E . 1990 Cell 63: 1167–1176

  • Peifer M, Orsulic S, Pai L and Loureiro J . 1993 Dev Suppl 163–176

  • Polakis P . 1999 Curr Opin Genet Dev 9: 15–21

  • Rubinfeld B, Souza B, Albert I, Munemitsu S and Polakis P . 1995 J Biol Chem 270: 5549–5555

  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S and Polakis P . 1996 Science 272: 1023–1026

  • Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P . 1997 Science 275: 1790–1792

  • Ruiz P, Brinkmann V, Ledermann B, Behrend M, Grund C, Thalhammer C, Vogel F, Birchmeier C, Gunthert U, Franke WW and Birchmeier W . 1996 J Cell Biol 135: 215–225

  • Sadot E, Simcha I, Shtutman M, Ben-Ze'ev A and Geiger B . 1998 Proc Natl Acad Sci USA 95: 15339–15344

  • Salomon D, Sacco PA, Guha-Roy S, Simcha I, Johnson KR, Wheelock MJ and Ben-Ze'ev A . 1997 J Cell Biol 139: 1325–1335

  • Sanson B, White P and Vincent J . 1996 Nature 383: 627–630

  • Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R and Ben-Ze'ev A . 1999 Proc Natl Acad Sci USA 96: 5522–5527

  • Simcha I, Geiger B, Yehuda-Levenberg S, Salomon D and Ben-Ze'ev A . 1996 J Cell Biol 133: 199–209

  • Simcha I, Shtutman M, Salomon D, Zhurinsky J, Sadot E, Geiger B and Ben-Ze'ev A . 1998 J Cell Biol 141: 1433–1448

  • Sommers C, Gelmann EP, Kemler R, Cowin P and Byers SW . 1994 Cancer Res 54: 3544–3552

  • Sparks A, Morin PJ, Vogelstein B and Kinzler KW . 1998 Cancer Res 58: 1130–1134

  • Spencer E, Jiang J and Chen ZJ . 1999 Genes Dev 13: 284–294

  • Tan P, Fuchs SY, Chen A, Wu K, Gomez C, Ronai Z and Pan Z-Q . 1999 Mol Cell 3: 527–533

  • Takeichi M . 1990 Annu Rev Biochem 59: 237–252

  • Takeichi M . 1995 Curr Opin Cell Biol 7: 619–627

  • Tetsu O and McCormick F . 1999 Nature 398: 422–426

  • Treier M, Staszewski LM and Bohmann D . 1994 Cell 78: 787–798

  • van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma AHD, Jones T, Bejsovec A, Peifer M, Mortin M and Clevers H . 1997 Cell 88: 789–799

  • Voeller H, Truica CI and Gelmann EP . 1998 Cancer Res 58: 2520–2523

  • Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ and Harper JW . 1999 Genes Dev 13: 270–283

  • Wodarz A and Nusse R . 1998 Annu Rev Cell Dev Biol 14: 59–88

  • Yamamoto H, Kishida S, Uochi T, Ikeda S, Koyama S, Asashima M and Kikuchi A . 1998 Mol Cell Biol 18: 2867–2875

  • Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F and Ben-Neriah Y . 1998 Nature 396: 590–594

  • Yost C, Torres M, Miller J, Huang E, Kimelman D and Moon R . 1996 Genes Dev 10: 1443–1454

  • Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek T, Perry W, Lee J, Tilghman S, Gumbiner B and Costantini F . 1997 Cell 90: 181–192

  • Zhou P and Howley . 1998 Mol Cell 2: 571–580

  • Zurawel R, Chiappa SA, Alle C and Raffel C . 1998 Cancer Res 58: 896–899

Download references

Acknowledgements

This study was supported by grants from the German-Israeli Foundation for Scientific Research and Development (A Ben-Ze'ev) the Cooperation Program in Cancer Research between DKFZ and IMOSA (A Ben-Ze'ev and B Geiger), by the Yad Abraham Center for Cancer Diagnosis and Therapy and the Minerva Foundation (B Geiger). A Ben-Ze'ev holds the Lunenfeld-Kunin Chair in Cell Biology and Genetics. B Geiger. Is the incumbent of the Erwin Neter chair in Cell and Tumor Biology.

Author information

Authors and Affiliations

  1. Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Einat Sadot, Inbal Simcha, Benjamin Geiger & Avri Ben-Ze'ev

  2. Department of Molecular and System Biology, Kyoto University, Yoshida-Konoe-ChoSakyo-ku, 606-8501, Kyoto, Japan

    Kazuhiro Iwai

  3. Faculty of Medicine and the Rappaport Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa, 31096, Israel

    Aaron Ciechanover

Authors
  1. Einat Sadot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inbal Simcha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Iwai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aaron Ciechanover
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Benjamin Geiger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Avri Ben-Ze'ev
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sadot, E., Simcha, I., Iwai, K. et al. Differential interaction of plakoglobin and β-catenin with the ubiquitin-proteasome system. Oncogene 19, 1992–2001 (2000). https://doi.org/10.1038/sj.onc.1203519

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203519

Keywords

This article is cited by

Search

Advanced search

Quick links