Assen G. Marintchev, PhD
Assistant Professor
Boston University School of Medicine
Dept of Physiology & Biophysics

MS, Sofia University
PhD, University of Connecticut



Molecular Mechanisms of Eukaryotic Translation Initiation and its Regulation:

Control of protein synthesis (translation) is vital for cell proliferation and differentiation. Initiation of translation is typically rate-limiting and is the main target of regulation. In cancer cells, multiple components of the translation initiation machinery are up-regulated in response to the demand for high rates of protein synthesis. The potential of using inhibitors of translation initiation for anti-cancer therapy was demonstrated in recent years and currently presents an active area of research.

Translation initiation is the process of locating the correct translation start codon on the mRNA and the assembly of an active ribosome, ready for translation. It requires a number of eukaryotic translation initiation factors (eIFs) and consists of several steps: initiation complex assembly; binding to mRNA; scanning; start codon recognition; and finally joining of the large ribosomal subunit to form a ribosome with a bound initiator Met-tRNAi ready to translate the mRNA. The initiator Met-tRNAi is delivered to the ribosome as a complex with eIF2-GTP. One eIF2-GTP:Met-tRNAi complex is “consumed” in every translation initiation cycle, with release of eIF2-GDP and deacylated initiator tRNAi. Regeneration of the eIF2-GTP:Met-tRNAi complex from eIF2-GDP and Met-tRNAi is catalyzed by the nucleotide exchange factor (GEF) eIF2B (reviewed in Marintchev and Wagner, 2004).

Our work is focused on studying the architecture of the translation initiation complexes, the molecular mechanisms of key steps in the process, and their regulation. The long-term goal is to build a detailed mechanistic and quantitative model of translation initiation as a whole, and learn how to rationally manipulate the system for the purposes of cancer therapy and treatment of metabolic disorders. Two areas of particular interest are the coordination between start codon selection and ribosomal subunit joining, and the regeneration of the eIF2-GTP:Met-tRNAi complex.


Mechanisms of assembly and remodeling of human translation initiation complexes
09/25/2011 - 08/31/2017 (PI)
NIH/National Institute of General Medical Sciences
5R01GM095720-05

Design of target-specific libraries for fragment based drug discovery
06/01/2016 - 05/31/2017 (PI)
Acpharis, Inc. NIH NIGMS
1R43GM119901-01




Yr Title Project-Sub Proj Pubs
2015 Mechanisms of assembly and remodeling of human translation initiation complexes 5R01GM095720-05 4
2014 Mechanisms of assembly and remodeling of human translation initiation complexes 5R01GM095720-04 4
2013 Mechanisms of assembly and remodeling of human translation initiation complexes 5R01GM095720-03 4
2012 Mechanisms of assembly and remodeling of human translation initiation complexes 5R01GM095720-02 4
2011 Mechanisms of assembly and remodeling of human translation initiation complexes 1R01GM095720-01 4
2010 Regulation of translation through the human translation initiation factor eIF5B 5K01CA119107-06 6
2009 Regulation of translation through the human translation initiation factor eIF5B 5K01CA119107-05 6
2008 Regulation of translation through the human translation initiation factor eIF5B 7K01CA119107-04 6
2008 Regulation of translation through the human translation initiation factor eIF5B 5K01CA119107-03 6
2007 Regulation of translation through the human translation initiation factor eIF5B 5K01CA119107-02 6
Showing 10 of 11 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Nag N, Lin KY, Edmonds KA, Yu J, Nadkarni D, Marintcheva B, Marintchev A. eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling. Nucleic Acids Res. 2016 Sep 06; 44(15):7441-56. PMID: 27325746; PMCID: PMC5009744; DOI: 10.1093/nar/gkw552;.
  2. Bogorad AM, Xia B, Sandor DG, Mamonov AB, Cafarella TR, Jehle S, Vajda S, Kozakov D, Marintchev A. Insights into the architecture of the eIF2Ba/ß/d regulatory subcomplex. Biochemistry. 2014 Jun 3; 53(21):3432-45.View Related Profiles. PMID: 24811713; PMCID: PMC4045321; DOI: 10.1021/bi500346u;.
  3. Marintchev A. Roles of helicases in translation initiation: a mechanistic view. Biochim Biophys Acta. 2013 Aug; 1829(8):799-809. PMID: 23337854; PMCID: PMC3640703; DOI: 10.1016/j.bbagrm.2013.01.005;.
  4. Marintchev, A. In: Dinman, J.D. (Ed.) Biophysical approaches to translational control of gene expression. Methods for studying the interactions of translation factors with the ribosome. Springer. New York, NY. 2013; 1:pp 83-101. View Publication
  5. Luna RE, Arthanari H, Hiraishi H, Nanda J, Martin-Marcos P, Markus MA, Akabayov B, Milbradt AG, Luna LE, Seo HC, Hyberts SG, Fahmy A, Reibarkh M, Miles D, Hagner PR, O'Day EM, Yi T, Marintchev A, Hinnebusch AG, Lorsch JR, Asano K, Wagner G. The C-terminal domain of eukaryotic initiation factor 5 promotes start codon recognition by its dynamic interplay with eIF1 and eIF2ß. Cell Rep. 2012 Jun 28; 1(6):689-702. PMID: 22813744; PMCID: PMC3401385; DOI: 10.1016/j.celrep.2012.04.007;.
  6. Marintchev A. Fidelity and quality control in gene expression. Preface. Adv Protein Chem Struct Biol. 2012; 86:ix. PMID: 22243586; DOI: 10.1016/B978-0-12-386497-0.00013-X;.
  7. Yu Y, Abaeva IS, Marintchev A, Pestova TV, Hellen CU. Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors. Nucleic Acids Res. 2011 Jun; 39(11):4851-65. PMID: 21306989; PMCID: PMC3113573; DOI: 10.1093/nar/gkr045;.
  8. Abaeva IS, Marintchev A, Pisareva VP, Hellen CU, Pestova TV. Bypassing of stems versus linear base-by-base inspection of mammalian mRNAs during ribosomal scanning. EMBO J. 2011 Jan 5; 30(1):115-29. PMID: 21113134; PMCID: PMC3020121; DOI: 10.1038/emboj.2010.302;.
  9. Yu Y, Marintchev A, Kolupaeva VG, Unbehaun A, Veryasova T, Lai SC, Hong P, Wagner G, Hellen CU, Pestova TV. Position of eukaryotic translation initiation factor eIF1A on the 40S ribosomal subunit mapped by directed hydroxyl radical probing. Nucleic Acids Res. 2009 Aug; 37(15):5167-82. PMID: 19561193; PMCID: PMC2731904; DOI: 10.1093/nar/gkp519;.
  10. Marintchev A, Edmonds KA, Marintcheva B, Hendrickson E, Oberer M, Suzuki C, Herdy B, Sonenberg N, Wagner G. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell. 2009 Feb 6; 136(3):447-60.View Related Profiles. PMID: 19203580; PMCID: PMC2656774; DOI: 10.1016/j.cell.2009.01.014;.
Showing 10 of 32 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 32 publications over 18 distinct years, with a maximum of 3 publications in 2003 and 2005 and 2008

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In addition to these self-described keywords below, a list of MeSH based concepts is available here.

Bioinformatics
Fluorescence anisotropy
FRET
NMR
Protein structure
Translation

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