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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. Pietsch EC, Perchiniak E, Canutescu AA, Wang G, Dunbrack RL, Murphy ME. Oligomerization of BAK by p53 utilizes conserved residues of the p53 DNA binding domain. J Biol Chem. 2008;283:21294-304. PubMed
2. Pietsch EC, Sykes SM, McMahon SB, Murphy ME. The p53 family and programmed cell death. Oncogene 2008;27:6507-21. PubMed
3. Humbey O, Pimkina J, Zilfou JT, Jarnik M, Dominguez-Brauer C, Burgess DJ, Eischen CM, Murphy ME. The ARF tumor suppressor can promote the progression of some tumors. Cancer Res. 2008;68:9608-9613. PubMed
4. Pimkina J, Humbey O, Zilfou JT, Jarnik M, Murphy ME. ARF induces autophagy by virtue of interation with and inhibition of Bcl-xl. J Biol Chem. 2009;284:2803-10.
5. Pimkina J, Murphy ME. ARF, autophagy and tumor suppression. Autophagy. 2009;5:1-3. PubMed