scholarly journals Fas-activated Ser/Thr phosphoprotein (FAST) is a eukaryotic initiation factor 4E-binding protein that regulates mRNA stability and cell survival

Translation ◽  
2013 ◽  
Vol 1 (1) ◽  
pp. e24047
Author(s):  
Wei Li ◽  
Pavel Ivanov ◽  
Paul Anderson
Keyword(s):  
Cell Survival ◽  
Mrna Stability ◽  
Binding Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

scholarly journals Cap-binding protein (eukaryotic initiation factor 4E) and 4E-inactivating protein BP-1 independently regulate cap-dependent translation.

1996 ◽  
Vol 16 (10) ◽  
pp. 5450-5457 ◽  
Author(s):  
D Feigenblum ◽  
R J Schneider
Keyword(s):  
Heat Shock ◽  
Translation Initiation ◽  
Binding Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Metaphase Arrest ◽  
Animal Cells ◽  
Eukaryotic Initiation Factor 4E ◽  
Dependent Protein

Cap-dependent protein synthesis in animal cells is inhibited by heat shock, serum deprivation, metaphase arrest, and infection with certain viruses such as adenovirus (Ad). At a mechanistic level, translation of capped mRNAs is inhibited by dephosphorylation of eukaryotic initiation factor 4E (eIF-4E) (cap-binding protein) and its physical sequestration with the translation repressor protein BP-1 (PHAS-I). Dephosphorylation of BP-I blocks cap-dependent translation by promoting sequestration of eIF-4E. Here we show that heat shock inhibits translation of capped mRNAs by simultaneously inducing dephosphorylation of eIF-4E and BP-1, suggesting that cells might coordinately regulate translation of capped mRNAs by impairing both the activity and the availability of eIF-4E. Like heat shock, late Ad infection is shown to induce dephosphorylation of eIF-4E. However, in contrast to heat shock, Ad also induces phosphorylation of BP-1 and release of eIF-4E. BP-1 and eIF-4E can therefore act on cap-dependent translation in either a mutually antagonistic or cooperative manner. Three sets of experiments further underscore this point: (i) rapamycin is shown to block phosphorylation of BP-1 without inhibiting dephosphorylation of eIF-4E induced by heat shock or Ad infection, (ii) eIF-4E is efficiently dephosphorylated during heat shock or Ad infection regardless of whether it is in a complex with BP-1, and (iii) BP-1 is associated with eIF-4E in vivo regardless of the state of eIF-4E phosphorylation. These and other studies establish that inhibition of cap-dependent translation does not obligatorily involve sequestration of eIF-4E by BP-1. Rather, translation is independently regulated by the phosphorylation states of eIF-4E and the 4E-binding protein, BP-1. In addition, these results demonstrate that BP-1 and eIF-4E can act either in concert or in opposition to independently regulate cap-dependent translation. We suggest that independent regulation of eIF-4E and BP-1 might finely regulate the efficiency of translation initiation or possibly control cap-dependent translation for fundamentally different purposes.

scholarly journals An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc.

1996 ◽  
Vol 16 (9) ◽  
pp. 4754-4764 ◽  
Author(s):  
R M Jones ◽  
J Branda ◽  
K A Johnston ◽  
M Polymenis ◽  
M Gadd ◽  
...  
Keyword(s):  
Electrophoretic Mobility ◽  
Promoter Region ◽  
Binding Protein ◽  
Dominant Negative ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Mobility Shift ◽  
Gene Encoding ◽  
Eukaryotic Initiation Factor 4E ◽  
E Box

The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the m7 GpppN cap on mRNA, thereby initiating translation. eIF4E is essential and rate limiting for protein synthesis. Overexpression of eIF4E transforms cells, and mutations in eIF4E arrest cells in G, in cdc33 mutants. In this work, we identified the promoter region of the gene encoding eIF4E, because we previously identified eIF4E as a potential myc-regulated gene. In support of our previous data, a minimal, functional, 403-nucleotide promoter region of eIF4E was found to contain CACGTG E box repeats, and this core eIF4E promoter was myc responsive in cotransfections with c-myc. A direct role for myc in activating the eIF4E promoter was demonstrated by cotransfections with two dominant negative mutants of c-myc (MycdeltaTAD and MycdeltaBR) which equally suppressed promoter function. Furthermore, electrophoretic mobility shift assays demonstrated quantitative binding to the E box motifs that correlated with myc levels in the electrophoretic mobility shift assay extracts; supershift assays demonstrated max and USF binding to the same motif. cis mutations in the core or flank of the eIF4E E box simultaneously altered myc-max and USF binding and inactivated the promoter. Indeed, mutations of this E box inactivated the promoter in all cells tested, suggesting it is essential for expression of eIF4E. Furthermore, the GGCCACGTG(A/T)C(C/G) sequence is shared with other in vivo targets for c-myc, but unlike other targets, it is located in the immediate promoter region. Its critical function in the eIF4E promoter coupled with the known functional significance of eIF4E in growth regulation makes it a particularly interesting target for c-myc regulation.

scholarly journals Serotonin Increases Phosphorylation of Synaptic 4EBP through TOR, but Eukaryotic Initiation Factor 4E Levels Do Not Limit Somatic Cap-Dependent Translation in Aplysia Neurons

2006 ◽  
Vol 26 (22) ◽  
pp. 8586-8598 ◽  
Author(s):  
Matthew Carroll ◽  
John Dyer ◽  
Wayne S. Sossin
Keyword(s):  
Binding Protein ◽  
Aplysia Californica ◽  
Memory Formation ◽  
Initiation Factor ◽  
Target Of Rapamycin ◽  
Phosphorylation Sites ◽  
Eukaryotic Initiation Factor ◽  
Cell Soma ◽  
Aplysia Neurons ◽  
Eukaryotic Initiation Factor 4E

ABSTRACT The target of rapamycin (TOR) plays an important role in memory formation in Aplysia californica. Here, we characterize one of the downstream targets of TOR, the eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP) from Aplysia. Aplysia 4EBP contains the four critical phosphorylation sites regulated by TOR as well as an N-terminal RAIP motif and a C-terminal TOS site. Aplysia 4EBP was hypophosphorylated in synaptosomes, and serotonin addition caused a rapamycin-sensitive increase in 4EBP phosphorylation both in synaptosomes and in isolated neurites. Aplysia 4EBP was regulated in a fashion similar to that of mammalian 4EBPs, binding to eIF4E when dephosphorylated and releasing eIF4E after phosphorylation. Overexpression of 4EBP in the soma of Aplysia neurons caused a specific decrease in cap-dependent translation that was rescued by concomitant overexpression of eIF4E. However, eIF4E overexpression by itself did not increase cap-dependent translation, suggesting that increasing levels of free eIF4E by phosphorylating 4EBP is not important in regulating cap-dependent translation in the cell soma. Total levels of eIF4E were also regulated by 4EBP, suggesting that 4EBP can also act as an eIF4E chaperone. These studies demonstrate the conserved nature of 4EBP regulation and its role in cap-dependent translation and suggest differential roles of 4EBP phosphorylation in the soma and synapse.

Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein

2019 ◽  
Vol 120 (9) ◽  
pp. 14201-14212 ◽  
Author(s):  
Asiya Batool ◽  
Sabreena Aashaq ◽  
Khurshid I. Andrabi
Keyword(s):  
Binding Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E
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