Lyn tyrosine kinase inhibits nuclear export of the p53 tumor suppressor.
The p53 tumor suppressor is activated in the cellular response to stress. Mdm2 inhibits p53-dependent transactivation and promotes degradation of p53 by the ubiquitin-proteosome pathway. The present studies demonstrate that p53 binds directly to the nuclear Lyn tyrosine kinase. Lyn increases p53 levels and stimulates p53-mediated transcription by a kinase-independent ... mechanism. The results also demonstrate that Lyn increases nuclear levels of ubiquitinated p53 by inhibiting export of p53 to the cytoplasm. In concert with these results, Lyn reverses Mdm2-mediated degradation of p53 and increases p53-dependent apoptosis. Our findings support a previously undefined role for nuclear Lyn in both activation and Mdm2-mediated regulation of p53.
Mesh Terms:
Active Transport, Cell Nucleus, Apoptosis, Cell Nucleus, Cytoplasm, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Glutathione Transferase, Humans, Immunoblotting, Luciferases, Microscopy, Confocal, Nuclear Proteins, Plasmids, Precipitin Tests, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Recombinant Fusion Proteins, Transcriptional Activation, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Ubiquitin, src-Family Kinases
Active Transport, Cell Nucleus, Apoptosis, Cell Nucleus, Cytoplasm, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Glutathione Transferase, Humans, Immunoblotting, Luciferases, Microscopy, Confocal, Nuclear Proteins, Plasmids, Precipitin Tests, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Recombinant Fusion Proteins, Transcriptional Activation, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Ubiquitin, src-Family Kinases
Cancer Biol. Ther.
Date: Mar. 19, 2003
PubMed ID: 12642697
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