Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):E3274-81. doi: 10.1073/pnas.1505297112. Epub 2015 Jun 8.

Protein synthesis during cellular quiescence is inhibited by phosphorylation of a translational elongation factor.

Author information

1
Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
2
Department of Chemistry, Columbia University, New York, NY 10027.
3
Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; jonathan.dworkin@columbia.edu.

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.

KEYWORDS:

EF-Tu; GTPase; Ser/Thr kinase; dormancy; sporulation

PMID:
26056311
PMCID:
PMC4485140
DOI:
10.1073/pnas.1505297112
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center