CONTRIBUTIONS AND MECHANISMS OF FOXO TRANSCRIPTION FACTORS ON THE PI3K PATHWAY
Andrea Salinas, Megan Keniry, Itzel Flores, Lilia Sanchez, Cristina Rodriguez, Neftali Vazquez, Rebecca Marks, Jesse Hirschmann.
University of Texas Pan-American, Edinburg, TX.
The conserved phosphatidylinositol 3 kinase (PI3K pathway) impacts cellular growth, metabolism, and survival. PI3K is a lipid kinase that catalyzes the production of phosphatidylinositol 3,4,5 trisphosphate (PIP3), which in turn binds to and activates targets such as the protein kinase AKT. Over 20 substrates have been characterized for AKT; arguably the best studied AKT substrates are the Forkhead subfamily O (FOXO) transcription factors: FOXO1, FOXO3, and FOXO4. AKT phosphorylates FOXO1, 3, and 4 on conserved amino acids, leading to their cytoplasmic retention/inactivation. Canonically, FOXO transcription factors induce genes that promote cell cycle arrest and apoptosis. However, one or more of these factors promotes PI3K output via a homeostatic feedback mechanism. The purpose of this poster is to addresses the mechanisms, contributions, and differences between FOXO1, 3, and 4. FOXO1 on PI3K pathway signals transduction. Currently, we are taking loss of function and gain of function approaches to delineate the specific contributions of each FOXO factor on the PI3K output (in mammalian cell lines, mouse embryonic fibroblast, and established human cell lines). We are utilizing western blot analysis and quantitative reverse transcript PCR to examine PI3K output. Excitingly, we are finding that FOXO factors have unique contributions to PI3K.