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Our research is focused on two cell death pathways, apoptosis and autophagy. We found that these two processes are mediated by two critical tumor suppressor genes, p53 and p14ARF. Data from our laboratory and others indicates that p53 suppresses tumor development in part through its ability to induce apoptosis. In cells in which DNA damage has occurred, and/or that sustain prolonged activation of mitogenic signals, p53 protein becomes stabilized and induces apoptosis. We are particularly interested in the impact of coding region polymorphisms in p53 and its ability to induce apoptosis. We recently found that the p14ARF tumor induces an alternate form of programmed cell death, called autophagy. Together, apoptosis and autophagy are the cell’s number one defense mechanisms against cancer. An enhanced understanding of how these two proteins normally defend against cancer will lead to improved avenues of cancer therapy.

1. Frank AK, Leu JI, Zhou Y, Devarajan K, Nedelko T, Klein-Szanto A, Hollstein M, Murphy ME. The codon 72 polymorphism of p53 regulates interaction with NF-{kappa}B and transactivation of genes involved in immunity and inflammation. Mol Cell Biol. 2011 Mar;31(6):1201-13.PubMed
2. Azzam GA, Frank AK, Hollstein M, Murphy ME. Tissue-specific apoptotic effects of the p53 codon 72 polymorphism in a mouse model. Cell Cycle. 2011 May 1;10(9):1352-5. PubMed
3. Frank AK, Pietsch EC, Dumont P, Tao J, Murphy ME. Wild-type and mutant p53 proteins interact with mitochondrial caspase-3. Cancer Biol Ther. 2011 April 15;11(8):740-5. PubMed
4. Leu JI, Pimkina J, Frank A, Murphy ME, and George DL. A Small Molecule Inhibitor of Inducible Heat Shock Protein 70 (HSP70). Mol Cell. 2009 Oct 9;36:15-27. PubMed
5. Pimkina J, Humbey O, Zilfou JT, Jarnik M, Murphy ME. ARF Induces Autophagy by Virtue of Interaction with Bcl-xl. J Biol Chem. 2009 Jan 30;284(5):2803-10. PubMed