Disease relevance of Eif4g1

• Infection of cells by foot-and-mouth disease virus (FMDV) causes the rapid inhibition of cellular cap-dependent protein synthesis that results from cleavage of the translation initiation factor eIF4G, a component of the cap-binding complex eIF4F [1].
• Finally, treatment of myotubes with PD-98059 or dnMEK1 adenovirus before TNF + INS addition resulted in a derepression of protein synthesis and the association of eIF4G with eIF4E [2].
• In the present work, cleavage of both eIF4GI and eIF4GII has been analyzed by employing the proteases encoded within the genomes of several members of the family Retroviridae, e.g., Moloney murine leukemia virus (MoMLV), mouse mammary tumor virus, human T-cell leukemia virus type 1, HIV-2, and simian immunodeficiency virus [3].
• The eIF4GI hydrolysis patterns obtained with HIV-1 and HIV-2 proteases were very similar to each other but rather different from those obtained with MoMLV protease [3].

High impact information on Eif4g1

• In addition, both Pdcd4 and Pdcd4(D418A) bound to the middle region of eIF4G [4].
• It has been proposed that binding of the eukaryotic translation initiation factor 4E (eIF-4E) to the inhibitory protein 4BP-1 blocks translation by preventing access of eIF-4G to the 5' cap of the mRNA [5].
• The cleavage of eIF4GI, which specifically needs caspase-3 activity, is dispensable for the inhibition of translation in MCF-7 cells [6].
• In addition, the stimulatory effect of eIF4G on the cap recognition of eIF4E is inhibited by the translational repressor, 4E-BP1 [7].
• Activation of a temperature-sensitive form of mouse p53 in murine erythroleukaemia cells rapidly inhibits protein synthesis and causes early dephosphorylation and cleavage of protein synthesis initiation factor eIF4GI and the eIF4E-binding protein 4E-BP1 [8].

Biological context of Eif4g1

• The signal for translation initiation is thought to involve phosphorylation of 4BP-1, which causes it to dissociate from eIF-4E and allows eIF-4G to localize to the 5' cap [5].
• This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding complex) and poly(A) binding protein (PABP) [9].
• NAC and DPI also inhibited phosphorylation of 4E-BP1 on Thr46 and association of eIF4E with eIF4G, steps that are important in the initiation phase of mRNA translation [10].
• Both full-length and N-terminally truncated eIF4G transfectants of NIH3T3 cells formed colonies in soft agar and increased the saturation density of cell growth, indicating that both eIF4Gs function similarly [11].
• The inhibition of translation is associated with specific cleavages of polypeptide chain initiation factors eIF4GI and eIF4B, a phenomenon previously observed in cells induced to undergo apoptosis in response to other stimuli [12].

Anatomical context of Eif4g1

• When bound to 4E-BP1, eIF4E cannot bind to eIF4G to form the active eIF4F complex, an event that is required for the binding of mRNA to the ribosome [13].
• All of the retroviral proteases examined were able to cleave the initiation factor eIF4GI both in intact cells and in cell-free systems, albeit with different efficiencies [3].

Associations of Eif4g1 with chemical compounds

• The amount of serine 1108-phosphorylated eIF4G (but not Ser209-phosphorylated eIF4E) was induced following PH [14].
• Leucine also increased the association of the initiation factors eIF4E and eIF4G, but did not affect the activity of the guanine nucleotide exchange factor eIF2B, nor total protein synthesis [15].

Physical interactions of Eif4g1

• Enhancement of the eIF4E affinity for cap occurs after binding to eIF4G peptides [16].

Other interactions of Eif4g1

• Insulin and IGF-I increased the amount of eIF4G associated with eIF4E in nutrient-deprived C2C12 myotubes [17].
• Caerulein inhibited the two major regulatory points of translation initiation: the activity of the guanine nucleotide exchange factor eIF2B (with an increase of eIF2alpha phosphorylation) and the formation of the eIF4F complex due, in part, to degradation of eIF4G [18].
• The role of eIF4G during the initiation of protein synthesis was studied using mouse mammary carcinoma FM3A cells and FM4G cells that overproduce an N-terminally truncated form of eIF4G, which lacks the binding site of poly(A)-binding protein [11].
• The Pdcd4 protein has weak homology to the eucaryotic translation initiation factor eIF4G and has been shown to interact with certain translation initiation factors [19].
• In addition, eIF2B epsilon, eIF4G1, and p70 S6 kinase protein levels decreased progressively with increasing recirculation time [20].

References