Mechanism and Regulation of Eukaryotic Protein Synthesis
We study the mechanism and regulation of protein synthesis, focusing on GTPases, protein kinases, translation factors and mRNA features that control this fundamental cellular process. We use molecular-genetic and biochemical studies in yeast and human cells to dissect the structure-function properties of translation factors, elucidate mechanisms that control protein synthesis, and characterize how mutations in the protein synthesis apparatus cause human disease. Of special interest are the translation initiation factors eIF2, a GTPase that binds methionyl-tRNA to the ribosome, and eIF5B, a second GTPase that catalyzes ribosomal subunit joining in the final step of translation initiation. We also investigate stress-responsive protein kinases that phosphorylate eIF2alpha, viral regulators of these kinases, and how cellular phosphatases are targeted to dephosphorylate eIF2alpha. We are characterizing eIF2gamma mutations that are associated with MEHMO syndrome, a novel X-linked intellectual disability syndrome, and we are investigating the function of the translation factor eIF5A with a focus on its ability to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates such as proline. We are also examining the role of the hypusine modification on eIF5A and the role of this factor in polyamine-regulated gene-specific translational control mechanisms, and we are characterizing metabolite control of translation via non-canonical upstream open reading frames (uORFs) in select mRNAs.
Dr. Thomas Dever is head of the Section on Protein Biosynthesis in the Division of Molecular and Cellular Biology of the NICHD, a position he has held since 1994. Dr. Dever received his B.S. in Chemistry from Gannon University, Erie, Pennsylvania in 1984. He received his Ph.D. in Biochemistry in 1990 from Case Western Reserve University in Cleveland, Ohio where he initiated his studies on eukaryotic translation in the laboratory of Dr. William Merrick. He studied as a postdoctoral fellow in the laboratory of Dr. Alan Hinnebusch in the NICHD from 1990 to 1994. Since 1994 he has headed the Section on Protein Biosynthesis. He is an elected fellow of the American Association for the Advancement of Sciences (AAAS) and the American Academy of Microbiology (AAM), and he serves on the advisory board of the journal Molecular Cell.
- Young-Baird SK, Lourenço MB, Elder MK, Klann E, Liebau S, Dever TE. Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB. Mol Cell. 2020;77(4):875-886.e7.
- Shin BS, Ivanov IP, Kim JR, Cao C, Kinzy TG, Dever TE. eEF2 diphthamide modification restrains spurious frameshifting to maintain translational fidelity. Nucleic Acids Res. 2023;51(13):6899-6913.
- Ivanov IP, Saba JA, Fan CM, Wang J, Firth AE, Cao C, Green R, Dever TE. Evolutionarily conserved inhibitory uORFs sensitize Hox mRNA translation to start codon selection stringency. Proc Natl Acad Sci U S A. 2022;119(9).
- Vindu A, Shin BS, Choi K, Christenson ET, Ivanov IP, Cao C, Banerjee A, Dever TE. Translational autoregulation of the S. cerevisiae high-affinity polyamine transporter Hol1. Mol Cell. 2021;81(19):3904-3918.e6.
- Ivanov IP, Shin BS, Loughran G, Tzani I, Young-Baird SK, Cao C, Atkins JF, Dever TE. Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing. Mol Cell. 2018;70(2):254-264.e6.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on Monday, October 30, 2023