Dissecting p53 tumor suppressor functions in vivo

Schmitt, C. A., Fridman, J. S., Yang, M., Baranov, E., Hoffman, R. M., Lowe, S. W. (April 2002) Dissecting p53 tumor suppressor functions in vivo. Cancer Cell, 1 (3). pp. 289-298. ISSN 1535-6108

URL: http://www.ncbi.nlm.nih.gov/pubmed/12086865
DOI: 10.1016/S1535-6108(02)00047-8

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: April 2002
Date Deposited: 31 Oct 2013 16:23
Last Modified: 31 Oct 2013 16:23
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28784

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