P19 ARF-p53 Tumor Suppressor Pathway During Oncogene-Induced Apoptosis and Senescence
Annual rept. 15 May 1999-15 May 2000
COLD SPRING HARBOR LAB OF QUANTITATIVE BIOLOGY NY
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The primary objective of this project is to provide new insights into the role of the p53 and ARF tumor suppressors in cancer development and therapy. During the first year of this study, we found that different oncogenes can promote different p53 post-translational modifications. Oncogene ras promotes phosphorylation of p53 on Serine 15, however, ElA does not. These data suggested that different oncogenes induce different phenotypes through different p53 post-translational modifications. It seems that p19ARF is required for p53 modifications, since p53 can not be phosphorylated on Ser 15 following Ras overexpression in ARF null cells. We also examined the impact of INK4aARF mutations on tumor development and therapy using the E micro-myc transgenic mouse. Our results clearly showed that inactivation of the INK4aARF locus accelerated Myc-induced lymphomagenesis, leading to massively disseminated lymphomas that displayed markedly reduced apoptosis. In collaboration with C. Sherr, we tried to produce different monoclonal antibodies to p19ARF Right now, we are doing the secondary screens to determine the antibodies specificity.
- Medicine and Medical Research