count	source_label	source_id	relationship	target_label	target_id	entity_type	solr_id	publication_id	sentences
6	EF3A_YEAST	UNIPROT:P16521	decreases		UNIPROT:P05198	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	As found above, under starvation conditions eEF3 overexpression significantly reduced the amount of eIF2α-P levels by a factor of about 5 (Fig. 3,E,lanes 2and3 versus lanes 5and6, andF).|||As shown above, eEF3 overexpression in aGCN1+strain reduced the amount of eIF2α phosphorylation under replete as well as starved conditions (Fig. 7,BandC,lanes 5and6 versus lanes 7and8;D; andE), and as reported previously the M7A mutation reduced the levels of eIF2α phosphorylation (Fig. 7,BandC,lanes 3and4 versus lanes 7and8;D, andE) (13).|||We again found that eEF3 overexpression reduced eIF2α-P levels even under replete conditions, by a factor of 6.7, to 15% of that of the wild-type control overexpressing GST alone (Fig. 3,E,lane 1 versus lane 4, andF).|||Interestingly, we found that even under nutrient-replete conditions, eEF3 overexpression reduced eIF2α-P levels, by a factor of 4.5, to 22% of that of the wild-type control overexpressing GST alone (Fig. 3,CandD).
6	EF3A_YEAST	UNIPROT:P16521	inhibits		UNIPROT:Q92616	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	If eEF3 impairs GAAC function by inhibiting Gcn1, and not by, for example, stimulating an eIF2α-P phosphatase or preventing eIF2α kinase domains from accessing their substrate, then, in contrast to Gcn2c, the Slg−phenotype elicited by PKR should not be diminished by eEF3 overexpression.|||Overexpression of the eEF3 HEAT Domain, or the eEF3 C-terminal Domain (CTD), Is Sufficient for Impairing Gcn2 Activation If eEF3 overexpression impairs Gcn1 function on the ribosome, then the ribosome binding activity of eEF3 must be essential for affecting Gcn1 function in activating Gcn2.|||We found that eEF3 overexpression exacerbated the Gcn−phenotype of Gcn1-M7A and further reduced the eIF2α phosphorylation levels of agcn1-M7Astrain, supporting the idea that eEF3 inhibits Gcn1 function on the ribosome.|||Although eEF3 would prevent Gcn1-mediated delivery of tRNAsdeacyl, for example the ones naturally occurring during the translation elongation cycle, to Gcn2, eEF1A would ensure that Gcn2 does not phosphorylate its substrate.|||Considering that the combined effect of the M7A mutation and eEF3 overexpression on cell growth in the presence of 3AT was clearly stronger than that of M7A or eEF3 overexpression alone, this indicates that the M7A mutation exacerbated the 3ATsphenotype associated with eEF3 overexpression, strongly supporting the idea that eEF3 overexpression impairs Gcn1 function on the ribosome.|||Thus, eEF3 overexpression might compete with only one or a few ribosome interaction site(s) in Gcn1 and thereby impair Gcn1 function, whereas other ribosome-binding sites in Gcn1 would still support efficient Gcn1-ribosome interaction.
6	EF3A_YEAST	UNIPROT:P16521	inhibits		UNIPROT:Q9P2K8	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Overexpressed eEF3 Reduces eIF2α Phosphorylation Levels If it is true that eEF3 overexpression prevents Gcn2 activation and GAAC response, then this should be associated with reduced phosphorylation levels of eIF2α, the substrate of Gcn2.|||Taken together, our data provide strong evidence that eEF3 negatively regulates Gcn2 activation in a manner requiring the HEAT domain and/or requiring an accessory ribosome-binding domain at the eEF3 C terminus that is dispensable for eEF3 essential function in translation elongation (1,27).|||We cannot exclude the possibility that eEF3 overexpression prevents Gcn2 function by a mechanism different to that proposed above.|||The Growth Defect Associated with Gcn2cIs Partially Suppressed by eEF3 Overexpression Having found that eEF3 overexpression leads to 3ATs, we wished to find additional genetic evidence that does not involve the usage of drugs that supports our idea that eEF3 overexpression impairs Gcn2 activation.|||Taken together, our results strongly suggest that eEF3 overexpression inhibits Gcn2 activation in response to amino acid limitation but also under replete conditions.|||To test our prediction that eEF3 affects Gcn1 function and thus impairs Gcn2 activation, we introduced into the yeast wild-type strain H1511 a plasmid expressing GST-tagged eEF3 from a galactose-inducible promoter or a plasmid harboring GST alone.
4	EF3A_YEAST	UNIPROT:P16521	inhibits		GO:0006412	Phenotype	165c7e64-ab8f-11e6-90f5-001a4ae51247	PMC4567705	Assuming that aggregated translation factors are inactive, the observed aggregation of eIF2B, eIF4B/G, eEF3, or eRF1 would be individually sufficient to substantially reduce net protein synthesis (Firczuk et al., 2013).
4	EF3A_YEAST	UNIPROT:P16521	activates		FPLX:F:actin	ProteinFamily	ca195fc4-c8e8-11e5-a1fd-001a4ae51246	17660846	In comparison to uninfected control slides, nonpathogenic commensal strain EFC-1 induced minimal reorganization of F-actin, but not displacement of TJ protein ZO-1 or AJ protein E-cadherin (Figure 6).
2	EF3A_YEAST	UNIPROT:P16521	inhibits		UNIPROT:P05198	Protein	455dce62-c46c-11e5-a92e-001a4ae51246	24732012	Overexpression of eEF3 leads to reduced eIF2α phosphorylation even under replete conditions[140].
2	EF3A_YEAST	UNIPROT:P16521	inhibits		UNIPROT:Q92616	Protein	455dce62-c46c-11e5-a92e-001a4ae51246	24732012	However, polysome co-sedimentation studies indicate that eEF3 overexpression does not reduce Gcn1–ribosome interaction, suggesting that eEF3 does not remove Gcn1 from the ribosome.
2	EF3A_YEAST	UNIPROT:P16521	inhibits		FPLX:GST	ProteinFamily	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	We again found that eEF3 overexpression reduced eIF2α-P levels even under replete conditions, by a factor of 6.7, to 15% of that of the wild-type control overexpressing GST alone (Fig. 3,E,lane 1 versus lane 4, andF).
2	EF3A_YEAST	UNIPROT:P16521	activates		UNIPROT:P62495	Protein	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	Our data showed that eEF3 also stimulates the esterase activity of eRF1 (Fig. 6).|||eEF3 stimulates the esterase activity of eRF1 and eRF3 Since UAA stop codon readthrough was facilitated by removal of eEF3 (Figs.
2	EF3A_YEAST	UNIPROT:P16521	dephosphorylatesProtein		UNIPROT:P05198	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Under starvation conditions, eEF3 overexpression in theGCN1+strain reduced eIF2α phosphorylation 2.05-fold; however, in agcn1-M7Astrain, eIF2α phosphorylation was reduced even further, 2.58-fold as compared with thegcn1-M7Astrain overexpressing GST alone (Fig. 7E), and this difference was even more pronounced under replete conditions (Fig. 7D).|||For example eEF3 could prevent the Gcn2 kinase domain from accessing and phosphorylating eIF2α, or eEF3 could promote eIF2α dephosphorylation by activating a phosphatase.
2	EF3A_YEAST	UNIPROT:P16521	activates		GO:0009058	Phenotype	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	eEF3 was also observed to stimulate luciferase synthesis with Control S30 (compare closed circles with closed squares,Fig. 2B).|||As stated above, the luciferase synthesis coded for by downstream ORF in the bicistronic mRNA was stimulated by removal of eEF3 only when it was in the same frame as the upstream ORF.
2	EF3A_YEAST	UNIPROT:P16521	activates		IP:IPR000801	ProteinFamily	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	Our data showed that eEF3 also stimulates the esterase activity of eRF1 (Fig. 6).|||eEF3 stimulates the esterase activity of eRF1 and eRF3 Since UAA stop codon readthrough was facilitated by removal of eEF3 (Figs.
2		CHEBI:16761	activates	EF3A_YEAST	UNIPROT:P16521	Chemical	2f749afa-c8df-11e5-9cb8-001a4ae51247	16954224	ADP Enhances the Association of eEF3 with eEF1A—Because both eEF3 and eEF1A bind nucleotides, an enzyme-linked immunosorbent assay-based binding assay was developed to look at the effect of these molecules on the eEF1A-eEF3 interaction.
2		PF:PF09598	inhibits	EF3A_YEAST	UNIPROT:P16521	ProteinFamily	b76821bc-c479-11e5-8491-001a4ae51247	PMC3078733	"Second, since Stm1 limits the interaction of eEF3 with
                      ribosomes, the reduction in translation could be due to eEF3 no longer interacting sufficiently with the ribosome.|||Alternatively, since Stm1 limits the interaction of eEF3 with ribosomes (Van Dyke et al. 2009), Stm1 might indirectly block translation through inhibition of eEF3 function."
1	EF3A_YEAST	UNIPROT:P16521	phosphorylatesProtein		UNIPROT:P05198	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	As shown above, eEF3 overexpression in aGCN1+strain reduced the amount of eIF2α phosphorylation under replete as well as starved conditions (Fig. 7,BandC,lanes 5and6 versus lanes 7and8;D; andE), and as reported previously the M7A mutation reduced the levels of eIF2α phosphorylation (Fig. 7,BandC,lanes 3and4 versus lanes 7and8;D, andE) (13).
1	EF3A_YEAST	UNIPROT:P16521	activates		UNIPROT:P68104	Protein	a6bf9ec0-3b5b-11e8-9fbf-001a4a160176	PMC5754060	eEF3 also stimulates eEF1A-mediated binding of cognate aa-tRNA to the A-site [5,6] potentially through a direct interaction with eEF1A.
1	EF3A_YEAST	UNIPROT:P16521	activates		UNIPROT:P68104	Protein	b39e193c-c47f-11e5-a92e-001a4ae51246	PMC2890720	"eEF3 stimulates eEF1A-dependent binding of a cognate aminoacyl-tRNA to the A site, and is involved in the release of deacylated
                            tRNA from the ribosomal E (exit) site (14)."
1	EF3A_YEAST	UNIPROT:P16521	activates		UNIPROT:O80339	Protein	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	eEF3 stimulates the esterase activity of eRF1 and eRF3 Since UAA stop codon readthrough was facilitated by removal of eEF3 (Figs.
1	EF3A_YEAST	UNIPROT:P16521	inhibits		UNIPROT:A8DRH7	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	If eEF3 impairs GAAC function by inhibiting Gcn1, and not by, for example, stimulating an eIF2α-P phosphatase or preventing eIF2α kinase domains from accessing their substrate, then, in contrast to Gcn2c, the Slg−phenotype elicited by PKR should not be diminished by eEF3 overexpression.
1	EF3A_YEAST	UNIPROT:P16521	increases		UNIPROT:P16521	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Considering the fact that on one hand eEF3 overexpression lead to a drastic—at least 4.5-fold—reduction of Gcn2 function in phosphorylating eIF2α (Fig. 3,CandD), but on the other hand eEF3 overexpression barely affected Gcn1-ribosome or Gcn2-ribosome interaction, this suggests that inhibition of Gcn2 function is not simply due to eEF3 removing Gcn1 from the ribosome.
1	EF3A_YEAST	UNIPROT:P16521	activates		GO:0006412	Phenotype	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	Results eEF3 stimulates translation of monocistronic mRNA and upstream ORF in bicistronic mRNA Since eEF3 is an essential gene, instead of creating yeast lacking it, we removed some of eEF3 from yeast S30 extract by anti-eEF3 beads (we called this extract “Rm-eEF3 S30”).
1	EF3A_YEAST	UNIPROT:P16521	activates		GO:0006414	Phenotype	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	The stimulation of translation elongation by eEF3 is negatively regulated by stress-related protein Stm1, a repressor of translation [39,40].
1	EF3A_YEAST	UNIPROT:P16521	activates		GO:0043200	Phenotype	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Taken together, our results strongly suggest that eEF3 overexpression inhibits Gcn2 activation in response to amino acid limitation but also under replete conditions.
1	EF3A_YEAST	UNIPROT:P16521	activates		FPLX:GST	ProteinFamily	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Interestingly, we found that eEF3 overexpression led to reduced growth in presence of 3AT (3AT sensitivity, 3ATs) as compared with the strain overexpressing GST alone (Fig. 1, comparefirstandsecond rows), suggesting that GAAC response is impaired by eEF3 overexpression.
1	EF3A_YEAST	UNIPROT:P16521	activates		IP:IPR013657	ProteinFamily	eb571b68-c867-11ee-9aaa-0050569a1f61	10.1016/j.abb.2023.109580	We examined whether removal of eEF3 stimulates readthrough of the premature stop codon UAA within an ORF.
1		FPLX:GST	inhibits	EF3A_YEAST	UNIPROT:P16521	ProteinFamily	bc7ac3ea-bbef-11e5-8abe-001a4ae51246	10.1016/j.phytochem.2012.04.016	In a subsequent step, this GST triple mutant served as a material to inactivate theGRX1(YCL035c) andTEF4(YKL081w,EFC1), again via the use of pUG73 and pUG72 (URA3 marker) for homologous recombination, respectively.
1		FPLX:Actin	activates	EF3A_YEAST	UNIPROT:P16521	ProteinFamily	ef33a07c-b0c6-11e7-b059-001a4a160175	PMC5640253	After cessation of r-protein or eEF3 synthesis actin polarization waned.
1		UNIPROT:Q9P2K8	activates	EF3A_YEAST	UNIPROT:P16521	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Overexpressed eEF3 Reduces eIF2α Phosphorylation Levels If it is true that eEF3 overexpression prevents Gcn2 activation and GAAC response, then this should be associated with reduced phosphorylation levels of eIF2α, the substrate of Gcn2.
1		UNIPROT:P16521	increases	EF3A_YEAST	UNIPROT:P16521	Protein	ead8470e-c481-11e5-85e4-001a4ae51246	PMC3488051	Considering the fact that on one hand eEF3 overexpression lead to a drastic—at least 4.5-fold—reduction of Gcn2 function in phosphorylating eIF2α (Fig. 3,CandD), but on the other hand eEF3 overexpression barely affected Gcn1-ribosome or Gcn2-ribosome interaction, this suggests that inhibition of Gcn2 function is not simply due to eEF3 removing Gcn1 from the ribosome.