Abstract
In this article, we identify and characterize p600, a unique 600-kDa retinoblastoma protein- and calmodulin-binding protein. In the nucleus, p600 and retinoblastoma protein seem to act as a chromatin scaffold. In the cytoplasm, p600 and clathrin form a meshwork structure, which could contribute to cytoskeletal organization and membrane morphogenesis. Reduced expression of p600 with interference RNA abrogates integrin-mediated ruffled membrane formation and, furthermore, prevents activation of integrin-mediated survival pathways. Consequently, knockdown of p600 sensitizes cells to apoptosis induced by cell detachment. These findings provide mechanistic insight into the regulation of membrane-proximal events in tumorigenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology
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Calmodulin / metabolism*
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Calmodulin-Binding Proteins / genetics
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Calmodulin-Binding Proteins / metabolism*
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Cell Membrane / physiology*
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Cell Surface Extensions / metabolism
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Cell Surface Extensions / ultrastructure
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Cell Survival*
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Cell Transformation, Neoplastic
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Cells, Cultured
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Enzyme Activation
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Humans
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Integrins / metabolism
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Binding
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RNA Interference
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Retinoblastoma Protein / metabolism*
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Ubiquitin-Protein Ligases
Substances
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Calmodulin
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Calmodulin-Binding Proteins
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Cytoskeletal Proteins
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Integrins
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Nuclear Proteins
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Retinoblastoma Protein
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UBR4 protein, human
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Ubiquitin-Protein Ligases