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Dissecting p53 tumor suppressor functions in vivo

Item Type:Article
Title:Dissecting p53 tumor suppressor functions in vivo
Creators Name:Schmitt, C.A. and Fridman, J.S. and Yang, M. and Baranov, E. and Hoffman, R.M. and Lowe, S.W.
Abstract:Although the p53 tumor suppressor acts in a plethora of processes that influence cellular proliferation and survival, it remains unclear which p53 functions are essential for tumor suppression and, as a consequence, are selected against during tumor development. Using a mouse model harboring primary, genetically modified myc-driven lymphomas, we show that disruption of apoptosis downstream of p53 by Bcl2 or a dominant-negative caspase 9 confers-like p53 loss-a selective advantage, and completely alleviates pressure to inactivate p53 during lymphomagenesis. Despite their p53-null-like aggressive phenotype, apoptosis-defective lymphomas that retain intact p53 genes do not display the checkpoint defects and gross aneuploidy that are characteristic of p53 mutant tumors. Therefore, apoptosis is the only p53 function selected against during lymphoma development, whereas defective cell-cycle checkpoints and aneuploidy are mere byproducts of p53 loss.
Keywords:Aneuploidy, Apoptosis, Caspase 9, Caspases, Cell Cycle, Cell Division, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, Cytochrome c Group, Neoplastic Gene Expression Regulation, Dominant Genes, Tumor Suppressor Genes, cdc Genes, myc Genes, Green Fluorescent Proteins, Homozygote, Luminescent Proteins, Lung, Lymphoma, Mutation, Experimental Neoplasms, Ploidies, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Protein p53, Animals, Mice
Source:Cancer Cell
Publisher:Cell Press / Elsevier
Page Range:289-298
Date:1 April 2002
Official Publication:https://doi.org/10.1016/S1535-6108(02)00047-8
PubMed:View item in PubMed

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