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Exploring Chromatin-Bound Mdm2 Functions In Compromised Transcriptional Regulation Of P53 Target Genes, Melissa Rosso
Exploring Chromatin-Bound Mdm2 Functions In Compromised Transcriptional Regulation Of P53 Target Genes, Melissa Rosso
Dissertations, Theses, and Capstone Projects
MDM2 overexpression is a common occurrence in many types of cancer. A single nucleotide polymorphism (T to G) near the mdm2 promoter, termed mdm2 SNP309, leads to MDM2 overexpression. This polymorphism is associated with accelerated tumor formation, decreased sensitivity to DNA damage treatment and compromised p53 transcriptional activity. Two G/G SNP309 cancer cell lines MANCA and A875, a Burkitts' lymphoma and melanoma respectively, express a stable wild-type p53 protein. We previously reported these cells have DNA damage resistant MDM2-p53 chromatin complexes and hypothesized that MDM2 is the contributing factor for the compromised p53 transcriptional activity. We created constitutive mdm2 shRNA …