Abstract
In apoptosis the tumor suppressor p53 and the c-myc proto-oncogene are usually up-regulated. We show a novel alternative pathway of apoptosis in human primary cells that is mediated by transcriptionally dependent decreases in p53 and c-Myc and decreases in p21. This pathway is regulated by the alternatively spliced V region and high-affinity heparin-binding domain of fibronectin. Requirements for c-Myc, p53, and p21 signals in maintaining survival and for their decreases in inducing apoptosis were demonstrated by the ability of p53, c-Myc, and p21 ectopic expression to rescue this apoptotic phenotype, and the ability of p53-deficient and c-myc antisense conditions to trigger a faster rate of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis*
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Blotting, Northern
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Blotting, Western
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Cell Line
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Cells, Cultured
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Chloramphenicol O-Acetyltransferase / metabolism
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Down-Regulation
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Fibroblasts / metabolism
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Fibronectins / chemistry
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Fibronectins / metabolism*
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Heparin / chemistry*
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Humans
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Oligonucleotides, Antisense / pharmacology
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Phenotype
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-myc / metabolism*
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Proto-Oncogene Proteins p21(ras) / metabolism
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RNA / metabolism
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Recombinant Proteins / metabolism
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Time Factors
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Transfection
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Fibronectins
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MAS1 protein, human
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Oligonucleotides, Antisense
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-myc
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Recombinant Proteins
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Tumor Suppressor Protein p53
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RNA
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Heparin
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Chloramphenicol O-Acetyltransferase
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)