In many malignant cells, both the anchorage requirement for survival and the function of the p53 tumor suppressor gene are subverted. These effects are consistent with the hypothesis that survival signals from extracellular matrix (ECM) suppress a p53-regulated cell death pathway. We report that survival signals from fibronectin are transduced by the focal adhesion kinase (FAK). If FAK or the correct ECM is absent, cells enter apoptosis through a p53-dependent pathway activated by protein kinase C λ/ι and cytosolic phospholipase A2. This pathway is suppressible by dominant-negative p53 and Bcl2 but not CrmA. Upon inactivation of p53, cells survive even if they lack matrix signals or FAK. This is the first report that p53 monitors survival signals from ECM/FAK in anchorage- dependent cells.
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19 October 1998
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October 19 1998
Extracellular Matrix Survival Signals Transduced by Focal Adhesion Kinase Suppress p53-mediated Apoptosis
Duško Ilić,
Duško Ilić
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
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Eduardo A.C. Almeida,
Eduardo A.C. Almeida
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
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David D. Schlaepfer,
David D. Schlaepfer
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
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Paul Dazin,
Paul Dazin
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
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Shinichi Aizawa,
Shinichi Aizawa
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
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Caroline H. Damsky
Caroline H. Damsky
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
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Duško Ilić
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
Eduardo A.C. Almeida
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
David D. Schlaepfer
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
Paul Dazin
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
Shinichi Aizawa
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
Caroline H. Damsky
*Departments of Stomatology and Anatomy, ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0512; § The Scripps Research Institute, Department of Immunology, La Jolla, California 92037; and ‖Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan
Duško Ili ć and Eduardo A.C. Almeida contributed equally to this work.
Address all correspondence to Caroline H. Damsky, Ph.D, University of California San Francisco, 513 Parnassus Avenue, HSW-604, San Francisco, CA 94143-0512. Tel.: (415) 476-8922. Fax: (415) 502-7338. E-mail: [email protected]
Received:
August 01 1998
Revision Received:
September 03 1998
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1998
J Cell Biol (1998) 143 (2): 547–560.
Article history
Received:
August 01 1998
Revision Received:
September 03 1998
Citation
Duško Ilić, Eduardo A.C. Almeida, David D. Schlaepfer, Paul Dazin, Shinichi Aizawa, Caroline H. Damsky; Extracellular Matrix Survival Signals Transduced by Focal Adhesion Kinase Suppress p53-mediated Apoptosis . J Cell Biol 19 October 1998; 143 (2): 547–560. doi: https://doi.org/10.1083/jcb.143.2.547
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