E2F1 TRANSCRIPTION FACTOR MODULATES TRANSLATION INITIATION

REAL SEBASTIAN; TAULER ALBERT

Carlos Paz

Congreso; XLIV ANUAL MEETING ARGENTINIAN SOCIETY FOR BIOCHEMESTRY AND MOLECULAR BIOLOGY; 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

E2F1 has been shown to induce both proliferation and apoptosisthrough transcription regulation of several essential genes involvedin these processes. In this study, we demonstrated that E2F1 couldalso modulate the translation initiation by a mechanism via p70S6kinase and eIF-4E binding protein-1. By using ER-E2F1 system,we demonstrate that translocation of E2F1 to the nucleus by theaddition of tamoxifen induces the phosphorylation of p70S6 kinaseand eIF-4E binding protein. PI 3-kinase inhibitor, LY294002, andmTOR inhibitor, rapamycin, repress this effect, suggesting theinvolvement of PI 3-kinase/mTOR pathway in this effect.However, activation of PI 3-kinase activity, measured as rate ofPKB phosphorylation, was not detected after the addition oftamoxifen. Surprisingly, the phosphorylation of p70 S6 kinase doesnot depend on the transcription activity of E2F1, suggesting thatE2F1 activates translation initiation by a protein/proteininteraction mechanism. Works in progress is to study theinvolvement of TSC2-Rheb-mTOR pathway in this regulation.The results obtained in this study point out for the first time a role ofE2F1 on cell growth