J. Cell Biol., Volume 139, Number 3, November 3, 1997 759-771

Dismantling Cell-Cell Contacts during Apoptosis Is Coupled to a Caspase-dependent Proteolytic Cleavage of -Catenin

Claudio Brancolini,^*§ Dean Lazarevic,^* Joe Rodriguez, and Claudio Schneider^*§

^* Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park, 34142 Trieste, Italy;  Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724; and ^§ Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia, Universita' di Udine, 33100 Udine, Italy

Cell death by apoptosis is a tightly regulated process that requires coordinated modification in cellular architecture. The caspase protease family has been shown to play a key role in apoptosis. Here we report that specific and ordered changes in the actin cytoskeleton take place during apoptosis.

In this context, we have dissected one of the first hallmarks in cell death, represented by the severing of contacts among neighboring cells. More specifically, we provide demonstration for the mechanism that could contribute to the disassembly of cytoskeletal organization at cell-cell adhesion. In fact, -catenin, a known regulator of cell-cell adhesion, is proteolytically processed in different cell types after induction of apoptosis. Caspase-3 (cpp32/apopain/yama) cleaves in vitro translated -catenin into a form which is similar in size to that observed in cells undergoing apoptosis. -Catenin cleavage, during apoptosis in vivo and after caspase-3 treatment in vitro, removes the amino- and carboxy-terminal regions of the protein. The resulting -catenin product is unable to bind -catenin that is responsible for actin filament binding and organization. This evidence indicates that connection with actin filaments organized at cell-cell contacts could be dismantled during apoptosis. Our observations suggest that caspases orchestrate the specific and sequential changes in the actin cytoskeleton occurring during cell death via cleavage of different regulators of the microfilament system.

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• Weng, Z., Xin, M., Pablo, L., Grueneberg, D., Hagel, M., Bain, G., Muller, T., Papkoff, J. (2002). Protection against Anoikis and Down-regulation of Cadherin Expression by a Regulatable beta -Catenin Protein. J. Biol. Chem. 277: 18677-18686 [Abstract] [Full Text]  
• Kolb, T. M., Chang, S. H., Davis, M. A. (2002). Biochemical and Morphological Events During Okadaic Acid-Induced Apoptosis of Tsc2-Null ERC-18 Cell Line. Toxicol Pathol 30: 235-246 [Abstract]  
• Sadot, E., Geiger, B., Oren, M., Ben-Ze'ev, A. (2001). Down-Regulation of {beta}-Catenin by Activated p53. Mol. Cell. Biol. 21: 6768-6781 [Abstract] [Full Text]  
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• Olivera, A., Kohama, T., Edsall, L., Nava, V., Cuvillier, O., Poulton, S., Spiegel, S. (1999). Sphingosine Kinase Expression Increases Intracellular Sphingosine-1-phosphate and Promotes Cell Growth and Survival. JCB 147: 545-558 [Abstract] [Full Text]  
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• Mills, J. C., Stone, N. L., Pittman, R. N. (1999). Extranuclear Apoptosis: The Role of the Cytoplasm in the Execution Phase. JCB 146: 703-708 [Abstract] [Full Text]  
• Orford, K., Orford, C. C., Byers, S. W. (1999). Exogenous Expression of {beta}-Catenin Regulates Contact Inhibition, Anchorage-independent Growth, Anoikis, and Radiation-induced Cell Cycle Arrest. JCB 146: 855-868 [Abstract] [Full Text]  
• Dinsdale, D., Zhuang, J., Cohen, G. M. (1999). Redistribution of Cytochrome c Precedes the Caspase-Dependent Formation of Ultracondensed Mitochondria, with a Reduced Inner Membrane Potential, in Apoptotic Monocytes. Am. J. Pathol. 155: 607-618 [Abstract] [Full Text]  
• Pervaiz, S., Seyed, M. A., Hirpara, J. L., Clement, M.-V., Loh, K. W. (1999). Purified Photoproducts of Merocyanine 540 Trigger Cytochrome C Release and Caspase 8-Dependent Apoptosis in Human Leukemia and Melanoma Cells. Blood 93: 4096-4108 [Abstract] [Full Text]  
• van de Water, B., Nagelkerke, J. F., Stevens, J. L. (1999). Dephosphorylation of Focal Adhesion Kinase (FAK) and Loss of Focal Contacts Precede Caspase-mediated Cleavage of FAK during Apoptosis in Renal Epithelial Cells. J. Biol. Chem. 274: 13328-13337 [Abstract] [Full Text]  
• Montagnoli, A., Fiore, F., Eytan, E., Carrano, A. C., Draetta, G. F., Hershko, A., Pagano, M. (1999). Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation. Genes Dev. 13: 1181-1189 [Abstract] [Full Text]  
• Pötter, E., Bergwitz, C., Brabant, G. (1999). The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues. Endocr. Rev. 20: 207-239 [Abstract] [Full Text]  
• WEBB, S. J., NICHOLSON, D., BUBB, V. J., WYLLIE, A. H. (1999). Caspase-mediated cleavage of APC results in an amino-terminal fragment with an intact armadillo repeat domain. FASEB J. 13: 339-346 [Abstract] [Full Text]  
• Wong, R. K., Baldwin, A. L., Heimark, R. L. (1999). Cadherin-5 redistribution at sites of TNF-alpha and IFN-gamma -induced permeability in mesenteric venules. Am. J. Physiol. Heart Circ. Physiol. 276: H736-H748 [Abstract] [Full Text]  
• Yamashita, K., Takahashi, A., Kobayashi, S., Hirata, H., Mesner, P. W. Jr, Kaufmann, S. H., Yonehara, S., Yamamoto, K., Uchiyama, T., Sasada, M. (1999). Caspases Mediate Tumor Necrosis Factor-alpha -Induced Neutrophil Apoptosis and Downregulation of Reactive Oxygen Production. Blood 93: 674-685 [Abstract] [Full Text]  
• Sgorbissa, A, Benetti, R, Marzinotto, S, Schneider, C, Brancolini, C (1999). Caspase-3 and caspase-7 but not caspase-6 cleave Gas2 in vitro: implications for microfilament reorganization during apoptosis. J. Cell Sci. 112: 4475-4482 [Abstract]  
• Korichneva, I, Hammerling, U (1999). F-actin as a functional target for retro-retinoids: a potential role in anhydroretinol-triggered cell death. J. Cell Sci. 112: 2521-2528 [Abstract]  
• Bannerman, D. D., Sathyamoorthy, M., Goldblum, S. E. (1998). Bacterial Lipopolysaccharide Disrupts Endothelial Monolayer Integrity and Survival Signaling Events through Caspase Cleavage of Adherens Junction Proteins. J. Biol. Chem. 273: 35371-35380 [Abstract] [Full Text]  
• Tesco, G., Kim, T.-W., Diehlmann, A., Beyreuther, K., Tanzi, R. E. (1998). Abrogation of the Presenilin 1/beta -Catenin Interaction and Preservation of the Heterodimeric Presenilin 1 Complex following Caspase Activation. J. Biol. Chem. 273: 33909-33914 [Abstract] [Full Text]  
• Kong, Y.-Y., Fischer, K.-D., Bachmann, M. F., Mariathasan, S., Kozieradzki, I., Nghiem, M. P., Bouchard, D., Bernstein, A., Ohashi, P. S., Penninger, J. M. (1998). Vav Regulates Peptide-specific Apoptosis in Thymocytes. JEM 188: 2099-2111 [Abstract] [Full Text]  
• Soini, Y., Paakko, P., Lehto, V-P. (1998). Histopathological Evaluation of Apoptosis in Cancer. Am. J. Pathol. 153: 1041-1053 [Full Text]  
• Takahashi, M., Mukai, H., Toshimori, M., Miyamoto, M., Ono, Y. (1998). Proteolytic activation of PKN by caspase-3 or related protease during apoptosis. Proc. Natl. Acad. Sci. USA 95: 11566-11571 [Abstract] [Full Text]  
• Canu, N., Dus, L., Barbato, C., Ciotti, M. T., Brancolini, C., Rinaldi, A. M., Novak, M., Cattaneo, A., Bradbury, A., Calissano, P. (1998). Tau Cleavage and Dephosphorylation in Cerebellar Granule Neurons Undergoing Apoptosis. J. Neurosci. 18: 7061-7074 [Abstract] [Full Text]  
• Cryns, V., Yuan, J. (1998). Proteases to die for. Genes Dev. 12: 1551-1570 [Full Text]  
• Steinhusen, U., Badock, V., Bauer, A., Behrens, J., Wittman-Liebold, B., Dorken, B., Bommert, K. (2000). Apoptosis-induced Cleavage of beta -Catenin by Caspase-3 Results in Proteolytic Fragments with Reduced Transactivation Potential. J. Biol. Chem. 275: 16345-16353 [Abstract] [Full Text]  
• Steinhusen, U., Weiske, J., Badock, V., Tauber, R., Bommert, K., Huber, O. (2001). Cleavage and Shedding of E-cadherin after Induction of Apoptosis. J. Biol. Chem. 276: 4972-4980 [Abstract] [Full Text]  
• Weiske, J., Schoneberg, T., Schroder, W., Hatzfeld, M., Tauber, R., Huber, O. (2001). The Fate of Desmosomal Proteins in Apoptotic Cells. J. Biol. Chem. 276: 41175-41181 [Abstract] [Full Text]  
• Li, P.-X., Wong, J., Ayed, A., Ngo, D., Brade, A. M., Arrowsmith, C., Austin, R. C., Klamut, H. J. (2000). Placental Transforming Growth Factor-beta Is a Downstream Mediator of the Growth Arrest and Apoptotic Response of Tumor Cells to DNA Damage and p53 Overexpression. J. Biol. Chem. 275: 20127-20135 [Abstract] [Full Text]  
• Mandala, S. M., Thornton, R., Galve-Roperh, I., Poulton, S., Peterson, C., Olivera, A., Bergstrom, J., Kurtz, M. B., Spiegel, S. (2000). Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death. Proc. Natl. Acad. Sci. USA 97: 7859-7864 [Abstract] [Full Text]  

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