eIF4E mediates suppression of apoptosis by regulation of IRES-dependent p53

GRECO HERNÁNDEZ,; PAULA VAZQUEZ PIANZOLA; DIEGO VAISMAN; PAOLA FERRERO; ROLANDO RIVERA POMAR

Bariloche - Río Negro - Argentina

Congreso; combined meetings: "Gene expression and RNA processing" "Cell biology, signaling and alternative splicing"; 2007

International Centre for Genetic Engineering and Biotechnology (ICGEB) - Fac de Cs Exactas y Naturales (UBA)? IFIBYNE-CONICET - Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT)

eIF4E mediates suppression of apoptosis by regulation of IRES-dependent p53 Greco Hernández1, Paula Vazquez-Pianzola2, Diego Vaisman3, Paola Ferrero3, Rolando Rivera-Pomar3 1 Mc Gill University, Montral, Canada; 2University of Bern, Bern, Switzerland; 3Centro Regional de Estudios Genomicos, Universidad Nacional de La Plata, La Plata Argentina (rrivera@creg.org.ar). Translational control during apoptosis is a finely tuned mechanism. p53 and the eukaryotic translation factor eIF4E play a key role in the regulation of apoptosis and cell proliferation. Both p53 and eIF4E have been linked to cancer, playing opposite roles. p53 is a tumor suppressor and eIF4E is a proto-oncogene. We show here that over-expression of Drosophila eIF4E-1 suppresses X-ray mediated apoptosis as well as p53-induced apoptosis in vivo. We demonstrate that p53 and eIF4E-1 interact genetically in vivo. We show that increased eIF4E levels result in a decrease of p53 and demonstrate that translation of p53 involves an IRES. In this context the function of eIF4E could be either suppressing p53 translation or increasing p53 degradation In mammals the level of p53 is in part regulated by mdm2, which has not been found in the Drosophila genome. We propose that eIF4E-1 might play an unpredicted role equivalent to mdm2 in apoptosis supression.