title: Protein synthesis during cellular quiescence is inhibited by phosphorylation of a translational elongation factor.
abstract: In nature, most organisms experience conditions that are suboptimal for growth. To survive, cells must fine-tune energy-demanding metabolic processes in response to nutrient availability. Here, we describe a novel mechanism by which protein synthesis in starved cells is down-regulated by phosphorylation of the universally conserved elongation factor Tu (EF-Tu). Phosphorylation impairs the essential GTPase activity of EF-Tu, thereby preventing its release from the ribosome. As a consequence, phosphorylated EF-Tu has a dominant-negative effect in elongation, resulting in the overall inhibition of protein synthesis. Importantly, this mechanism allows a quick and robust regulation of one of the most abundant cellular proteins. Given that the threonine that serves as the primary site of phosphorylation is conserved in all translational GTPases from bacteria to humans, this mechanism may have important implications for growth-rate control in phylogenetically diverse organisms.
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Sandro F F
authors.initials: SF
authors.lastname: Pereira
authors.affiliation: Department of Chemistry, Columbia University, New York, NY 10027.
authors.forename: Ruben L
authors.initials: RL
authors.lastname: Gonzalez
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; jonathan.dworkin@columbia.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dworkin
mesh_terms: D001412:Bacillus subtilis / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D010441:Peptide Chain Elongation, Translational; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013171:Spores, Bacterial
chemical_list: D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D010444:Peptide Elongation Factor Tu
keywords: EF-Tu; GTPase; Ser/Thr kinase; dormancy; sporulation