Tumor promotion by Mdm2 splice variants unable to bind p53

Fridman, J. S., Hernando, E., Hemann, M. T., de Stanchina, E., Cordon-Cardo, C., Lowe, S. W. (September 2003) Tumor promotion by Mdm2 splice variants unable to bind p53. Cancer Research, 63 (18). pp. 5703-5706. ISSN 0008-5472

URL: http://www.ncbi.nlm.nih.gov/pubmed/14522887

Abstract

The Mdm2 oncoprotein physically associates with p53 and antagonizes its tumor suppressor functions. Previous studies indicate that some tumors express alternatively or aberrantly spliced Mdm2 variants that are unable to bind p53, but whether these actively contribute to carcinogenesis or are a byproduct of cancer progression has been unclear. In this study, we examined the ability of full-length Mdm2 and several tumor-derived splice variants to modulate tumor development in Emu-myc transgenic mice. We report that several tumor-derived Mdm2 splice variants promote tumorigenesis in a manner that is comparable with full-length Mdm2. Our results imply that the current paradigm for understanding Mdm2 action during oncogenesis is incomplete, and its splice variants contribute to human cancer.

Item Type: Paper
Uncontrolled Keywords: MESSENGER-RNA P53-DEPENDENT APOPTOSIS HUMAN CANCER IN-VIVO ONCOGENE TRANSCRIPTS SUPPRESSOR LYMPHOMAGENESIS EXPRESSION MALIGNANCY
Subjects: diseases & disorders > cancer > cancer types > B cell lymphoma
diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons > exon splicing
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
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: September 2003
Date Deposited: 01 Apr 2013 20:22
Last Modified: 01 Apr 2013 20:22
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27987

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