scholarly journals Disruption of the Interaction of Mammalian Protein Synthesis Eukaryotic Initiation Factor 4B with the Poly(A)-binding Protein by Caspase- and Viral Protease-mediated Cleavages

2001 ◽  
Vol 276 (26) ◽  
pp. 23922-23928 ◽  
Author(s):  
Martin Bushell ◽  
Wendy Wood ◽  
Gillian Carpenter ◽  
Virginia M. Pain ◽  
Simon J. Morley ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Binding Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Viral Protease ◽  
Mammalian Protein

scholarly journals Nitric oxide mediates NMDA-induced persistent inhibition of protein synthesis through dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 and eukaryotic initiation factor 4G proteolysis

2008 ◽  
Vol 411 (3) ◽  
pp. 667-677 ◽  
Author(s):  
Valérie Petegnief ◽  
Míriam Font-Nieves ◽  
M. Elena Martín ◽  
Matilde Salinas ◽  
Anna M. Planas
Keyword(s):  
Nitric Oxide ◽  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Initiation Factor ◽  
Protein Synthesis Inhibition ◽  
Eukaryotic Initiation Factor ◽  
Translation Inhibition ◽  
Synthesis Inhibition ◽  
Nos Inhibitors

Cerebral ischaemia causes long-lasting protein synthesis inhibition that is believed to contribute to brain damage. Energy depletion promotes translation inhibition during ischaemia, and the phosphorylation of eIF (eukaryotic initiation factor) 2α is involved in the translation inhibition induced by early ischaemia/reperfusion. However, the molecular mechanisms underlying prolonged translation down-regulation remain elusive. NMDA (N-methyl-D-aspartate) excitotoxicity is also involved in ischaemic damage, as exposure to NMDA impairs translation and promotes the synthesis of NO (nitric oxide), which can also inhibit translation. In the present study, we investigated whether NO was involved in NMDA-induced protein synthesis inhibition in neurons and studied the underlying molecular mechanisms. NMDA and the NO donor DEA/NO (diethylamine–nitric oxide sodium complex) both inhibited protein synthesis and this effect persisted after a 30 min exposure. Treatments with NMDA or NO promoted calpain-dependent eIF4G cleavage and 4E-BP1 (eIF4E-binding protein 1) dephosphorylation and also abolished the formation of eIF4E–eIF4G complexes; however, they did not induce eIF2α phosphorylation. Although NOS (NO synthase) inhibitors did not prevent protein synthesis inhibition during 30 min of NMDA exposure, they did abrogate the persistent inhibition of translation observed after NMDA removal. NOS inhibitors also prevented NMDA-induced eIF4G degradation, 4E-BP1 dephosphorylation, decreased eIF4E–eIF4G-binding and cell death. Although the calpain inhibitor calpeptin blocked NMDA-induced eIF4G degradation, it did not prevent 4E-BP1 dephosphorylation, which precludes eIF4E availability, and thus translation inhibition was maintained. The present study suggests that eIF4G integrity and hyperphosphorylated 4E-BP1 are needed to ensure appropriate translation in neurons. In conclusion, our data show that NO mediates NMDA-induced persistent translation inhibition and suggest that deficient eIF4F activity contributes to this process.

scholarly journals Ischaemia induces changes in the association of the binding protein 4E-BP1 and eukaryotic initiation factor (eIF) 4G to eIF4E in differentiated PC12 cells

2000 ◽  
Vol 351 (2) ◽  
pp. 327-334 ◽  
Author(s):  
M. Elena MARTÍN ◽  
Francisco M. MUÑOZ ◽  
Matilde SALINAS ◽  
Juan L. FANDO
Keyword(s):  
Protein Synthesis ◽  
Pc12 Cells ◽  
Kinase Inhibitor ◽  
Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Eukaryotic Initiation Factor ◽  
Differentiated Pc12 Cells

Ischaemia was obtained in vitro by subjecting nerve-growth-factor-differentiated PC12 cells to glucose deprivation plus anoxia. During ischaemia the rate of protein synthesis was significantly inhibited, and eIF4E-binding protein (4E-BP1) and eukaryotic initiation factor 4E (eIF4E) were significantly dephosphorylated in parallel. In addition, ischaemia induced an enhancement of the association of 4E-BP1 to eIF4E, which in turn decreased eIF4F formation, whereas no degradation of initiation factor 4G was observed. The treatment of PC12 cells with the specific p38 mitogen-activated protein kinase inhibitor SB203580 induced eIF4E dephosphorylation but did not cause any effect on protein synthesis rate. Rapamycin, the inhibitor of mammalian target of rapamycin (‘mTOR’), but not PD98059, the inhibitor of extracellular signal-regulated protein kinases (‘ERK1/2’), induced similar effects on 4E-BP1 phosphorylation to ischaemia; nevertheless, 4E-BP1–eIF4E complex levels were higher in ischaemia than in rapamycin-treated cells. In addition, both protein synthesis rate and eIF4F formation were lower in ischaemic cells than in rapamycin-treated cells.

Insulin stimulates protein synthesis in skeletal muscle by enhancing the association of eIF-4E and eIF-4G

1997 ◽  
Vol 272 (2) ◽  
pp. C754-C759 ◽  
Author(s):  
S. R. Kimball ◽  
C. V. Jurasinski ◽  
J. C. Lawrence ◽  
L. S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Gastrocnemius Muscle ◽  
Binding Protein ◽  
Fold Increase ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Phosphorylated Form ◽  
Stimulation Of

Insulin stimulated protein synthesis in gastrocnemius muscle of perfused rat hindlimb preparations by approximately twofold. The stimulation of protein synthesis was associated with a 12-fold increase in the amount of eukaryotic initiation factor eIF-4G bound to the mRNA cap-binding protein eIF-4E. In part, the increased binding of eIF-4G to eIF-4E was a result of release of eIF-4E bound to the translational regulator, PHAS-I, through a mechanism involving enhanced phosphorylation of PHAS-I. However, the insulin-induced association of eIF-4E and eIF-4G was not due to increased net phosphorylation of eIF-4E because insulin decreased the amount present in the phosphorylated form from 86 to 59% of total eIF-4E. Overall, the results suggest that insulin stimulates protein synthesis in gastrocnemius muscle through a mechanism involving increased binding of eIF-4G to eIF-4E, which is in part due to phosphorylation of PHAS-I, resulting in a release of eIF-4E from the inactive PHAS-I x eIF-4E complex.

scholarly journals Effect of sepsis on eIE4E availability in skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. E1178-E1184 ◽  
Author(s):  
Thomas C. Vary ◽  
Scot R. Kimball
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Binding Protein ◽  
Abscess Formation ◽  
Sterile Inflammation ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Sterile Abscess ◽  
Inhibition Of Protein Synthesis

Chronic septic abscess formation causes an inhibition of protein synthesis in gastrocnemius that is not observed in rats with a sterile abscess. The inhibition is associated with an impaired translation initiation. The present study was designed to investigate the effects of sepsis on phosphorylation and availability of eukaryotic initiation factor (eIF)4E in gastrocnemius 5 days after induction of a sterile or septic abscess. Neither sepsis nor sterile inflammation altered the extent of eIF4E phosphorylation. Moreover, no changes in the amount of the binding protein 4E-BP1 associated with eIF4E or in the phosphorylation of 4E-BP1 were observed during sepsis or sterile inflammation. In contrast, sepsis and sterile inflammation caused a reduction in the relative amount of eIF4G bound to eIF4E compared with controls. The diminished amount of eIF4G bound to eIF4E was not the result of a reduced abundance of eIF4E. Sepsis, but not sterile inflammation, caused an increase in the cellular abundance of eIF4E. The results provide evidence that alterations in the eIF4E system are probably not rate controlling for the synthesis of total, mixed proteins in gastrocnemius during sepsis. Instead, on the basis of our previous studies, changes in eIF2B appear to be responsible for limiting protein synthesis in skeletal muscle during sepsis.

scholarly journals The mRNA-binding Protein YB-1 (p50) Prevents Association of the Eukaryotic Initiation Factor eIF4G with mRNA and Inhibits Protein Synthesis at the Initiation Stage

2003 ◽  
Vol 278 (16) ◽  
pp. 13936-13943 ◽  
Author(s):  
Maxim P. Nekrasov ◽  
Maria P. Ivshina ◽  
Konstantin G. Chernov ◽  
Elizaveta A. Kovrigina ◽  
Valentina M. Evdokimova ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Binding Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Mrna Binding Protein ◽  
Initiation Stage ◽  
Mrna Binding

Cytoskeletal proteins associate with components of the ribosomal maturation and translation apparatus in Xenopus stage I oocytes

Zygote ◽  
2014 ◽  
Vol 23 (5) ◽  
pp. 669-682 ◽  
Author(s):  
Loredana Chierchia ◽  
Margherita Tussellino ◽  
Domenico Guarino ◽  
Rosa Carotenuto ◽  
Nadia DeMarco ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Elongation Factor ◽  
Cytoskeletal Proteins ◽  
Stage I ◽  
Initiation Factor ◽  
Perinuclear Region ◽  
Eukaryotic Initiation Factor ◽  
Translation Apparatus ◽  
Ribosomal Stalk

SummaryActin-based cytoskeleton (CSK) and microtubules may bind to RNAs and related molecules implicated in translation. However, many questions remain to be answered regarding the role of cytoskeletal components in supporting the proteins involved in steps in the maturation and translation processes. Here, we performed co-immunoprecipitation and immunofluorescence to examine the association between spectrins, keratins and tubulin and proteins involved in 60S ribosomal maturation and translation in Xenopus stage I oocytes, including ribosomal rpl10, eukaryotic initiation factor 6 (Eif6), thesaurins A/B, homologs of the eEF1α elongation factor, and P0, the ribosomal stalk protein. We found that rpl10 and eif6 cross-reacted with the actin-based CSK and with tubulin. rpl10 co-localizes with spectrin, particularly in the perinuclear region. eif6 is similarly localized. Given that upon ribosomal maturation, the insertion of rpl10 into the 60S subunit occurs simultaneously with the release of eif6, one can hypothesise that actin-based CSK and microtubules provide the necessary scaffold for the insertion/release of these two molecules and, subsequently, for eif6 transport and binding to the mature 60S subunit. P0 and thesaurins cross-reacted with only spectrin and cytokeratins. Thesaurins aggregated at the oocyte periphery, rendering this a territory favourable site for protein synthesis; the CSK may support the interaction between thesaurins and sites of the translating ribosome. Moreover, given that the assembly of the ribosome stalk, where P0 is located, to the 60S subunit is essential for the release of eif6, it can be hypothesised that the CSK can facilitate the binding of the stalk to the 60S.

scholarly journals Phosphorylation of eukaryotic initiation factor 4E (eIF4E) at Ser209 is not required for protein synthesis in vitro and in vivo

2001 ◽  
Vol 268 (20) ◽  
pp. 5375-5385 ◽  
Author(s):  
Linda McKendrick ◽  
Simon J. Morley ◽  
Virginia M. Pain ◽  
Rosemary Jagus ◽  
Bhavesh Joshi
Keyword(s):  
Protein Synthesis ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E
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