• Parkhurst, Lawrence J (PI)
  • Gupta, Naba (PI)

Project: Research project

Project Details


DESCRIPTION This research will
study the molecular mechanism of peptide chain initiation in animal cells
and the roles of different factors in regulation of protein synthesis under
different physiological conditions, which include mitogen stimulation and
viral infection. The first step in peptide chain initiation is the
formation of a ternary complex between the eukaryotic peptide chain
initiation factor 2 (eIF-2), Met-tRNAf and GTP,MET-tRNA.f eIF-2-GTP. The
next step is the transfer of Met-tRNAf. 40S mRNA complex. An important
regulatory mechanism involves one or more eIF-2 kinases and an eIF-2 kinase
inhibitor (a 67 kDa polypeptide - p67). eIF-2 kinases phosphorylate eIF-2
and thus inhibit protein synthesis and the increased availability of p67
renders eIF-2 resistant to eIF-2 kinase phosphorylation and so promotes
protein synthesis in the presence of eIF-2 kinases. Objectives of the
research are: (1) Studies of the characteristics and factor requirements
for ternary and Met-tRNAf. 40S mRNA complex formation. Endeavors will be
made to extensively purify different protein factors and analyze their
roles and requirements in ternary and Met-tRNAf. 40smRNA complex
formation. Also, Drs. Hershey and Merrick agreed to supply peptide chain
initiation factors purified in their laboratories. The investigators will
also compare the factor preparation from all three laboratories (Gupta,
Hershey, Merrick) and arrive at a mutually agreeable definition regarding
the characteristics and requirements for these factors in ternary and
Met-tRNAf. 40S mRNA complex formation. (2) Studies of the regulation of
protein synthesis initiation. Emphasis will be given to the studies of the
roles of p67 and eIF-2 kinases in the regulatory process. Efforts will be
made to determine qualitative and quantitative changes in p67, eIF-2
kinases and other factor activities during mitogen stimulation, as well as
during polio viral infection. These changes will then be related to the
protein synthesis activities of the cells.
Effective start/end date5/1/7812/31/99


  • National Institutes of Health: $172,195.00


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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