Translational Regulation by CPEB in Cellular Senescence

Univ Of Massachusetts Med Sch Worcester, Worcester MA

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): Senescence is a tumor suppression mechanism that protects cells from unrestricted cell divisions in response to stress. The translational regulator CPEB is required for senescence in mouse embryonic fibroblasts (MEFs) since those derived from CPEB knockout mice are immortal. In addition, over-expression of CPEB causes wild type MEFs to senesce prematurely. These and other data suggest that CPEB could be a tumor suppressor. To investigate the molecular mechanism of CPEB-induced senescence, I propose the following aims: 1) test the hypothesis that CPEB must bind RNA and be phosphorylated on a key residue to induce senescence; 2) test the hypothesis that CPEB induces senescence through interactions with several factors that regulate polyadenylation-induced translation; 3) test the hypothesis that the translation of specific mRNAs, under the control of CPEB, are important for senescence. I will employ a combination of techniques include protein-protein analysis, RNA-protein co-immunoprecipitation, siRNA knockdowns, and measurement of mRNA polyadenylation. [unreadable] [unreadable] [unreadable]