The mdm-2 oncogene encodes a zinc finger protein composed of 491 amino acid residues. The amino terminal domain of mdm-2 (residues 16 - 120) bind to an inactivate the p53 transcription factor activity. Residues 200 - 300 in the mdm-2 protein binds the L5 ribosomal protein and 5SRNA while the zinc finger domain is localized between residues 300 - 491. Experiments have been designed to test whether the mdm-2 oncogene can transform cells when the target cells do not have the p53 gene or fail to produce the p53 protein. If overexpression of the mdm-2 protein in a cell with no p53 can enhance the tumorigenic potential of the cells, we will map the mdm-2 domains responsible for this phenotype. Experiments been formulated to identify putative genes regulated by mdm-2 in a cell, and a yeast two hybrid system is being utilized to identify proteins that can bind to and alter mdm-2 activities. The RNA-SELEX procedure is being utilized to determine if specific RNA sequences or structures will bind to mdm-2 protein and if so, to which domain of the protein. Cell lines in some complementation groups from Cockayne's syndrome (Cs-B) and Xeroderma pigmentosum (XP-A) will induce p53 in response to DNA damage, but fail to induce high levels of mdm-2 (a p53 responsive gene). Experiments are planned to determine the nature of this defect.

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Ferguson, Scott B; Blundon, Malachi A; Klovstad, Martha S et al. (2012) Modulation of gurken translation by insulin and TOR signaling in Drosophila. J Cell Sci 125:1407-19
Capra, John A; Laskowski, Roman A; Thornton, Janet M et al. (2009) Predicting protein ligand binding sites by combining evolutionary sequence conservation and 3D structure. PLoS Comput Biol 5:e1000585
Capra, John A; Singh, Mona (2008) Characterization and prediction of residues determining protein functional specificity. Bioinformatics 24:1473-80
Williams, Courtney M; Engler, Adam J; Slone, R Daniel et al. (2008) Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation. Cancer Res 68:3185-92
Banks, Eric; Nabieva, Elena; Chazelle, Bernard et al. (2008) Organization of physical interactomes as uncovered by network schemas. PLoS Comput Biol 4:e1000203
Sabourin, Michelle; Zakian, Virginia A (2008) ATM-like kinases and regulation of telomerase: lessons from yeast and mammals. Trends Cell Biol 18:337-46
Banks, Eric; Nabieva, Elena; Peterson, Ryan et al. (2008) NetGrep: fast network schema searches in interactomes. Genome Biol 9:R138
Klovstad, Martha; Abdu, Uri; Schupbach, Trudi (2008) Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint. PLoS Genet 4:e31
Clouse, K Nicole; Ferguson, Scott B; Schupbach, Trudi (2008) Squid, Cup, and PABP55B function together to regulate gurken translation in Drosophila. Dev Biol 313:713-24
Denef, Natalie; Chen, Yu; Weeks, Stephen D et al. (2008) Crag regulates epithelial architecture and polarized deposition of basement membrane proteins in Drosophila. Dev Cell 14:354-64

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