TY - JOUR
T1 - The guanine nucleotide-exchange factor, eIF-2B
AU - Price, N.
AU - Proud, C.
N1 - Funding Information:
Support for the work on elF-2B it) the authors" laboratory has been provided by the Medical Research Council, tile Science and Engineering Research Council and The Wellt:ome Trust. The authors are grateful to Jim Jefferson and his co-workers for allowing us to see their setit~ence data prior to publication We thank Sue OIdfield, Gavin Welsh and Bridget Jones for critical reading of this document.
PY - 1994
Y1 - 1994
N2 - Eukaryotic initiation factor eIF-2B catalyses the exchange of guanine nucleotides on another translation initiation factor, eIF-2, which itself mediates the binding of the initiator Met-tRNA to the 40S ribosomal subunit during translation initiation. eIF-2B promotes the release of GDP from inactive [eIF-2·GDP] complexes, thus allowing formation of the active [eIF-2·GTP] species which subsequently binds the Met-tRNA. This guanine nucleotide-exchange, step, and thus eIF-2B activity, are known to be an important control point for translation initiation. The activity of eIF-2B can be modulated in several ways. The best characterised of these involves the phosphorylation of the α-subunit of eIF-2 by specific protein kinases regulated by particular ligands. Phosphorylation of eIF-2α leads to inhibition of eIF-2B. This mechanism is involved in the control of translation under a variety of conditions, including amino acid deprivation in yeast (Saccharomyces cereviseae) where it causes translational upregulation of the transcription factor GCN4, and in virus-infected animal cells, where it involves a protein kinase activated by double-stranded RNA. There is now also growing evidence for direct regulation of eIF-2B. This appears likely to involve the phosphorylation of its largest subunit. Under certain circumstances eIF-2B may also be regulated by allosteric mechanisms. eIF-2B is a heteropentamer (subunits termed α, β, γ, δ and ε{lunate}) and is thus more complex than most other guanine nucleotide-exchange factors. The genes encoding all five subunits have been cloned in yeast (exploiting the GCN4 regulatory system): all but the α appear to be essential for eIF-2B activity. However, this subunit may confer sensitivity to eIF-2α phosphorylation. cDNAs encoding the α, β, δ and ε{lunate} subunits have been cloned from mammalian sources. There is substantial homology between the yeast and mammalian sequences. Attention is now directed towards understanding the roles of individual subunits in the function and regulation of eIF-2B.
AB - Eukaryotic initiation factor eIF-2B catalyses the exchange of guanine nucleotides on another translation initiation factor, eIF-2, which itself mediates the binding of the initiator Met-tRNA to the 40S ribosomal subunit during translation initiation. eIF-2B promotes the release of GDP from inactive [eIF-2·GDP] complexes, thus allowing formation of the active [eIF-2·GTP] species which subsequently binds the Met-tRNA. This guanine nucleotide-exchange, step, and thus eIF-2B activity, are known to be an important control point for translation initiation. The activity of eIF-2B can be modulated in several ways. The best characterised of these involves the phosphorylation of the α-subunit of eIF-2 by specific protein kinases regulated by particular ligands. Phosphorylation of eIF-2α leads to inhibition of eIF-2B. This mechanism is involved in the control of translation under a variety of conditions, including amino acid deprivation in yeast (Saccharomyces cereviseae) where it causes translational upregulation of the transcription factor GCN4, and in virus-infected animal cells, where it involves a protein kinase activated by double-stranded RNA. There is now also growing evidence for direct regulation of eIF-2B. This appears likely to involve the phosphorylation of its largest subunit. Under certain circumstances eIF-2B may also be regulated by allosteric mechanisms. eIF-2B is a heteropentamer (subunits termed α, β, γ, δ and ε{lunate}) and is thus more complex than most other guanine nucleotide-exchange factors. The genes encoding all five subunits have been cloned in yeast (exploiting the GCN4 regulatory system): all but the α appear to be essential for eIF-2B activity. However, this subunit may confer sensitivity to eIF-2α phosphorylation. cDNAs encoding the α, β, δ and ε{lunate} subunits have been cloned from mammalian sources. There is substantial homology between the yeast and mammalian sequences. Attention is now directed towards understanding the roles of individual subunits in the function and regulation of eIF-2B.
KW - exchange factor
KW - guanine nucleotide
KW - initiation factor
KW - protein phosphorylation
KW - translation
UR - http://www.scopus.com/inward/record.url?scp=0028582139&partnerID=8YFLogxK
U2 - 10.1016/0300-9084(94)90079-5
DO - 10.1016/0300-9084(94)90079-5
M3 - Article
C2 - 7893825
AN - SCOPUS:0028582139
VL - 76
SP - 748
EP - 760
JO - Biochimie
JF - Biochimie
SN - 0300-9084
IS - 8
ER -