Effects of Inhibitors of RNA and Protein Synthesis on the Subcellular Distribution of the Eukaryotic Translation Initiation Factor, eIF-5A, and the HIV-1 Rev Protein

Neurosignals ◽  
1997 ◽  
Vol 6 (3) ◽  
pp. 143-149 ◽  
Author(s):  
Xiao-Ping Shi ◽  
Kuo-Chang Yin ◽  
Lloyd Waxman
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Subcellular Distribution ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Rna And Protein Synthesis ◽  
Eukaryotic Translation Initiation ◽  
Hiv 1 ◽  
Rev Protein

scholarly journals Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2α

1999 ◽  
Vol 342 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Shinya SATOH ◽  
Makoto HIJIKATA ◽  
Hiroshi HANDA ◽  
Kunitada SHIMOTOHNO
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Caspase 3 ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Α Subunit ◽  
Eukaryotic Translation ◽  
Initiation Of Translation ◽  
Eukaryotic Translation Initiation

Eukaryotic translation initiation factor 2α (eIF-2α), a target molecule of the interferon-inducible double-stranded-RNA-dependent protein kinase (PKR), was cleaved in apoptotic Saos-2 cells on treatment with poly(I)˙poly(C) or tumour necrosis factor α. This cleavage occurred with a time course similar to that of poly(ADP-ribose) polymerase, a well-known caspase substrate. In addition, eIF-2α was cleaved by recombinant active caspase-3 in vitro. By site-directed mutagenesis, the cleavage site was mapped to an Ala-Glu-Val-Asp300 ↓ Gly301 sequence located in the C-terminal portion of eIF-2α. PKR phosphorylates eIF-2α on Ser51, resulting in the suppression of protein synthesis. PKR-mediated translational suppression was repressed when the C-terminally cleaved product of eIF-2α was overexpressed in Saos-2 cells, even though PKR can phosphorylate this cleaved product. These results suggest that caspase-3 or related protease(s) can modulate the efficiency of protein synthesis by cleaving the α subunit of eIF-2, a key component in the initiation of translation.

scholarly journals Resistance to Vesicular Stomatitis Virus Infection Requires a Functional Cross Talk between the Eukaryotic Translation Initiation Factor 2α Kinases PERK and PKR

2004 ◽  
Vol 78 (23) ◽  
pp. 12747-12761 ◽  
Author(s):  
Dionissios Baltzis ◽  
Li-Ke Qu ◽  
Stavroula Papadopoulou ◽  
Jaime D. Blais ◽  
John C. Bell ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Virus Infection ◽  
Vesicular Stomatitis Virus ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation ◽  
Vesicular Stomatitis ◽  
Eif2α Kinase

ABSTRACT Phosphorylation of the alpha (α) subunit of the eukaryotic translation initiation factor 2 (eIF2) leads to the inhibition of protein synthesis in response to diverse stress conditions, including viral infection. The eIF2α kinase PKR has been shown to play an essential role against vesicular stomatitis virus (VSV) infection. We demonstrate here that another eIF2α kinase, the endoplasmic reticulum-resident protein kinase PERK, contributes to cellular resistance to VSV infection. We demonstrate that mouse embryonic fibroblasts (MEFs) from PERK−/− mice are more susceptible to VSV-mediated apoptosis than PERK+/+ MEFs. The higher replication capacity of VSV in PERK−/− MEFs results from their inability to attenuate viral protein synthesis due to an impaired eIF2α phosphorylation. We also show that VSV-infected PERK−/− MEFs are unable to fully activate PKR, suggesting a cross talk between the two eIF2α kinases in virus-infected cells. These findings further implicate PERK in virus infection, and provide evidence that the antiviral and antiapoptotic roles of PERK are mediated, at least in part, via the activation of PKR.

scholarly journals The 39-kilodalton subunit of eukaryotic translation initiation factor 3 is essential for the complex's integrity and for cell viability in Saccharomyces cerevisiae.

1997 ◽  
Vol 17 (1) ◽  
pp. 145-153 ◽  
Author(s):  
T Naranda ◽  
M Kainuma ◽  
S E MacMillan ◽  
J W Hershey
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Initiation Phase ◽  
Eukaryotic Translation Initiation ◽  
Translation Initiation Factor 3

Eukaryotic translation initiation factor 3 (eIF3) in the yeast Saccharomyces cerevisiae comprises about eight polypeptides and plays a central role in the binding of methionyl-tRNAi and mRNA to the 40S ribosomal subunit. The fourth largest subunit, eIF3-p39, was gel purified, and a 12-amino-acid tryptic peptide was sequenced, enabling the cloning of the TIF34 gene. TIF34 encodes a 38,753-Da protein that corresponds to eIF3-p39 in size and antigenicity. Disruption of TIF34 is lethal, and depletion of eIF3-p39 by glucose repression of TIF34 expressed from a GAL promoter results in cessation of cell growth. As eIF3-p39 levels fall, polysomes become smaller, indicating a role for eIF3-p39 in the initiation phase of protein synthesis. Unexpectedly, depletion results in degradation of all of the subunit proteins of eIF3 at a rate much faster than the normal turnover rates of these proteins. eIF3-p39 has 46% sequence identity with the p36 subunit of human eIF3. Both proteins are members of the WD-repeat family of proteins, possessing five to seven repeat elements. Taken together, the results indicate that eIF3-p39 plays an important, although not necessarily direct, role in the initiation phase of protein synthesis and suggest that it may be required for the assembly and maintenance of the eIF3 complex in eukaryotic cells.

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