A novel role for p120 catenin in E-cadherin function (original) (raw)
Article| November 11 2002
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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3Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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2Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232
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2Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232
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3Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium
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3Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium
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1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
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Reneé C. Ireton
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Michael A. Davis
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Jolanda van Hengel
3Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium
Deborah J. Mariner
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Kirk Barnes
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Molly A. Thoreson
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Panos Z. Anastasiadis
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Linsey Matrisian
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Linda M. Bundy
2Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232
Linda Sealy
2Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232
Barbara Gilbert
3Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium
Frans van Roy
3Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium
Albert B. Reynolds
1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Address correspondence to Albert B. Reynolds, Dept. Cancer Biology, Vanderbilt University, 771 PRB, Nashville, TN 37232-6840. Tel.: (615) 343-9532. Fax: (615) 936-6399. E-mail: [email protected]
Abbreviations used in this paper: ARM, armadillo; IRES, internal ribosomal entry site; JMD, juxtamembrane domain; neo, neomycin resistance gene; p120, p120-catenin; PS, presenilin.
Received: May 23 2002
Revision Received: September 30 2002
Accepted: September 30 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 159 (3): 465–476.
Revision Received:
September 30 2002
Accepted:
September 30 2002
Citation
Reneé C. Ireton, Michael A. Davis, Jolanda van Hengel, Deborah J. Mariner, Kirk Barnes, Molly A. Thoreson, Panos Z. Anastasiadis, Linsey Matrisian, Linda M. Bundy, Linda Sealy, Barbara Gilbert, Frans van Roy, Albert B. Reynolds; A novel role for p120 catenin in E-cadherin function . _J Cell Biol 11 November 2002; 159 (3): 465–476. doi: https://doi.org/10.1083/jcb.200205115
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Îndirect evidence suggests that p120-catenin (p120) can both positively and negatively affect cadherin adhesiveness. Here we show that the p120 gene is mutated in SW48 cells, and that the cadherin adhesion system is impaired as a direct consequence of p120 insufficiency. Restoring normal levels of p120 caused a striking reversion from poorly differentiated to cobblestone-like epithelial morphology, indicating a crucial role for p120 in reactivation of E-cadherin function. The rescue efficiency was enhanced by increased levels of p120, and reduced by the presence of the phosphorylation domain, a region previously postulated to confer negative regulation. Surprisingly, the rescue was associated with substantially increased levels of E-cadherin. E-cadherin mRNA levels were unaffected by p120 expression, but E-cadherin half-life was more than doubled. Direct p120–E-cadherin interaction was crucial, as p120 deletion analysis revealed a perfect correlation between E-cadherin binding and rescue of epithelial morphology. Interestingly, the epithelial morphology could also be rescued by forced expression of either WT E-cadherin or a p120-uncoupled mutant. Thus, the effects of uncoupling p120 from E-cadherin can be at least partially overcome by artificially maintaining high levels of cadherin expression. These data reveal a cooperative interaction between p120 and E-cadherin and a novel role for p120 that is likely indispensable in normal cells.
The Rockefeller University Press
2002
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