Abstract
In addition to its proapoptotic function, caspase-8 is also important for several other processes, including suppressing necroptosis, cell migration, and immune cell survival. In the present study, we report that the loss of caspase-8 in B lymphocytes leads to B-cell malignancies and that the risk for these tumors is further enhanced in the absence of p53. We also report that deficiency of caspase-8 results in impaired cytokinesis and that casp8(-/-) lymphomas display remarkably elevated levels of chromosomal aberrations. Our data support an important role for caspase-8 in the maintenance of genomic integrity and highlight its tumor-suppressive function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Autoimmune Lymphoproliferative Syndrome / complications
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Autoimmune Lymphoproliferative Syndrome / genetics
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Autoimmune Lymphoproliferative Syndrome / immunology
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Autoimmune Lymphoproliferative Syndrome / pathology
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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B-Lymphocytes / physiology
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Caspase 8 / genetics
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Caspase 8 / physiology*
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Cells, Cultured
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Chromosomal Instability / genetics*
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Down-Regulation / genetics
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Down-Regulation / immunology
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Genes, p53 / physiology
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Genetic Predisposition to Disease
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Lymphoma, B-Cell / etiology
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Lymphoma, B-Cell / genetics*
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Lymphoma, B-Cell / mortality
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Lymphoma, B-Cell / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Survival Analysis
Substances
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Casp8 protein, mouse
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Caspase 8