Selenite Targets eIF4E-Binding Protein-1 to Inhibit Translation Initiation and Induce the Assembly of Non-Canonical Stress Granules

Stress granules (SGs) are large cytoplasmic ribonucleoprotein complexes that are assembled when cells are exposed to stress. SGs promote the survival of stressed cells by contributing to the reprogramming of protein expression as well as by blocking pro-apoptotic signaling cascades. These cytoprotective effects implicated SGs in the resistance of cancer cells to radiation and chemotherapy. We have found that sodium selenite, a selenium compound with chemotherapeutic potential, is a potent inducer of SG assembly. Selenite-induced SGs differ from canonical mammalian SGs in their morphology, composition and mechanism of assembly. Their assembly is induced primarily by eIF4E-binding protein1 (4EBP1)-mediated inhibition of translation initiation, which is reinforced by concurrent phosphorylation of eIF2α. Selenite-induced SGs lack several classical SG components, including proteins that contribute to pro-survival functions of canonical SGs. Our results reveal a new mechanism of mammalian SG assembly and provide insights into how selenite cytotoxicity may be exploited as an anti-neoplastic therapy

Speech Communication

Contains reports on four research projects.U. S. Air Force (Air Force Cambridge Research Center, Air Research and Development Command) under Contract AF19(604)-6102National Science Foundatio

Localized transverse bursts in inclined layer convection

We investigate a novel bursting state in inclined layer thermal convection in which convection rolls exhibit intermittent, localized, transverse bursts. With increasing temperature difference, the bursts increase in duration and number while exhibiting a characteristic wavenumber, magnitude, and size. We propose a mechanism which describes the duration of the observed bursting intervals and compare our results to bursting processes in other systems.Comment: 4 pages, 8 figure