Role of Translation Initiation Factor elF-2B in the Regulation of Protein Synthesis in Mammalian Cells

Scot R. Kimball, Harry Mellor, Kevin M. Flowers, Leonard S. Jefferson

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The importance of eIF-2B in the regulation of protein synthesis is highlighted by a number of studies reporting a change in its activity in response to various cellular perturbations. In many cases, the change in eIF-2B activity is a result of an increase in phosphorylation of the a-subunit of eIF-2. The activity of eIF-2B is regulated through a variety of mechanisms. This regulation is currently being studied in a number of species, including yeast, rat, rabbit, and human. This chapter derives a system based on a single species that can be used for the genetic analysis of the regulation of eIF-2B activity. The components of this system include not only the individual subunits of eIF-2 and eIF-2B, but also the kinase(s) and phosphatase(s) that are involved in regulating the phosphorylation state of the α-subunit of eIF-2 and the є-subunit of eIF-2B. Two eIF-2a kinases have been identified and characterized in mammalian cells—PKR and heme-controlled repressor (HCR). PKR has a clearly defined role in the cellular response to viral infection and a newly identified role in the response to the inhibition of protein processing in the endoplasmic reticulum. In addition, the regulation of HCR by heme in the cells of erythroid origin is well characterized.

Original languageEnglish (US)
Pages (from-to)165-196
Number of pages32
JournalProgress in Nucleic Acid Research and Molecular Biology
Volume54
Issue numberC
DOIs
StatePublished - Jan 1 1996

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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