count	source_label	source_id	relationship	target_label	target_id	entity_type	solr_id	publication_id	sentences
32	GCHFR	UNIPROT:P30047	activates		UNIPROT:P30793	Protein	3fbd7c68-3254-11e6-a3b4-001a4ae51246	10.1074/jbc.273.32.20102	Under these conditions, GFRP stimulated the activity of GTP cyclohydrolase I in a dose-dependent manner and leveled off at a concentration of 0.2 μm, which is the same concentration as that of GTP cyclohydrolase I contained in the reaction mixture (Fig.7).|||Positive cooperativity was found with respect to phenylalanine in the association of GFRP with GTP cyclohydrolase I and also in the GFRP-mediated stimulation of GTP cyclohydrolase I activity, whereas no cooperative phenomenon was observed for either BH4and GTP in the inhibitory complex formation.
32	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	3fbd7c68-3254-11e6-a3b4-001a4ae51246	10.1074/jbc.273.32.20102	Dose Dependence of GFRP for Its BH4-dependent Inhibitory Action on GTP Cyclohydrolase I Activity To determine the amount of GFRP required to totally inhibit GTP cyclohydrolase I, we examined the effect of varying amounts of GFRP on the activity of a fixed amount of GTP cyclohydrolase I (0.23 μm) in the presence of a saturating concentration of BH4(Fig.2).|||This result indicates that, as in the case of the GFRP-dependent inhibition of GTP cyclohydrolase I, an equimolar number of GFRP subunits is necessary for the total activation of GTP cyclohydrolase I activity, indicating that two molecules of GFRP are required for the total activation of one molecule of GTP cyclohydrolase I. To physically determine the protein stoichiometry of the stimulatory complex formed between GFRP and GTP cyclohydrolase I, we performed similar gel filtration experiments as for the inhibitory complex.|||This result indicates that, as in the case of the GFRP-dependent inhibition of GTP cyclohydrolase I, an equimolar number of GFRP subunits is necessary for the total activation of GTP cyclohydrolase I activity, indicating that two molecules of GFRP are required for the total activation of one molecule of GTP cyclohydrolase I. Protein Stoichiometry of the Stimulatory Complex Formation between GTP Cyclohydrolase I and GFRP To physically determine the protein stoichiometry of the stimulatory complex formed between GFRP and GTP cyclohydrolase I, we performed similar gel filtration experiments as for the inhibitory complex.|||To determine the amount of GFRP required to totally inhibit GTP cyclohydrolase I, we examined the effect of varying amounts of GFRP on the activity of a fixed amount of GTP cyclohydrolase I (0.23 μm) in the presence of a saturating concentration of BH4(Fig.2).|||Inhibitory Complex Formation To determine the amount of GFRP required to totally inhibit GTP cyclohydrolase I, we examined the effect of varying amounts of GFRP on the activity of a fixed amount of GTP cyclohydrolase I (0.23 μm) in the presence of a saturating concentration of BH4(Fig.2).
26		MESH:D008070	inhibits	GCHFR	UNIPROT:P30047	Phenotype	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	A dose of 0.1 pg/ml LPS was sufficient to cause a significant suppression of GFRP mRNA (p< 0.01, Student'sttest).|||LPS Down-regulates GFRP mRNA in THP-1 Cells, in HUVEC, and in Rat Tissues Next we studied expression of GFRP mRNA in conditions known to induce GTP cyclohydrolase I by Northern blot in THP-1 cells in relation to glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Fig.2A).|||We present evidence that GFRP is down-regulated by bacterial lipopolysaccharide (LPS) in cultured human cells and in ratsin vivo, thus rendering tetrahydrobiopterin biosynthesis independent of metabolic control by phenylalanine.
20		MESH:D009569	decreases	GCHFR	UNIPROT:P30047	Phenotype	285158cc-cb2c-11e5-8189-001a4ae51246	12359727	These effects of BH4and phenylalanine suggest that NO may suppress GFRP level in hepatocytes.|||This suggests that the suppression of GFRP expression by NO is a mechanism to amplify NO production and protect hepatocytes from injury during acute inflammatory states.|||These results suggest that NO may suppress the cellular level or biological activity of GFRP.
16	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	285158cc-cb2c-11e5-8189-001a4ae51246	12359727	GTPCHI activity can be post-translationally inhibited by BH4in the presence of GFRP, and this inhibition is reversed by phenylalanine (31).
16		MESH:D008070	decreases	GCHFR	UNIPROT:P30047	Phenotype	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	While interferon-γ alone had no effect on the expression of GFRP (97 ± 31% of control), LPS (37 ± 15% of control) and interferon-γ plus LPS (42 ± 16% of control) significantly (p< 0.05, Student'sttest) suppressed GFRP expression in THP-1 cells.
16		UNIPROT:P01579	decreases	GCHFR	UNIPROT:P30047	Protein	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	While interferon-γ alone had no effect on the expression of GFRP (97 ± 31% of control), LPS (37 ± 15% of control) and interferon-γ plus LPS (42 ± 16% of control) significantly (p< 0.05, Student'sttest) suppressed GFRP expression in THP-1 cells.
14		CHEBI:17295	activates	GCHFR	UNIPROT:P30047	Chemical	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	l-Phenylalanine Stimulates Human Recombinant GTP Cyclohydrolase I in the Presence of GFRP Since all work on the action of GFRP had been done thus far with rat enzymes, and since we wanted to study GFRP expression in human cells, we first cloned and expressed human GFRP and studied its action on human recombinant GTP cyclohydrolase I.
8	GCHFR	UNIPROT:P30047	inhibits		MESH:D001708	Phenotype	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Previous work by others showed that by decreasing GFRP, biopterin production is stimulated in different cell types[19,32].|||Cells overexpressing GFRP demonstrated significantly low biopterin levels after 48 h transfection, indicating that GFRP decreases biopterin synthesis in the cells.
8		MESH:D008070	activates	GCHFR	UNIPROT:P30047	Phenotype	6bc2127e-0b71-11f0-b759-0050569a791b	10.1016/S1016-8478(23)10719-9	According toKalivendiet al. (2005), lipopolysaccharide (LPS) stimulated the increase of GTPCH and decrease of GFRP.
4	GCHFR	UNIPROT:P30047	activates		UNIPROT:P30793	Protein	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Together these results indicate that stimulation of biopterin synthesis by LPS involves signaling of GFRP, which by releasing GTPCH-I from allosteric inhibition increases biopterin synthesis in the cell.
4	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	50f72826-bc02-11e5-8abe-001a4ae51246	10.1016/j.niox.2006.04.160	GTPCH feedback regulatory protein (GFRP) mediates the feedback inhibition of GTPCH by tetrahydrobiopterin, as well as the stimulation of GTPCH by phenylalanine.
4	GCHFR	UNIPROT:P30047	activates		GO:0009058	Phenotype	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Together these results indicate that stimulation of biopterin synthesis by LPS involves signaling of GFRP, which by releasing GTPCH-I from allosteric inhibition increases biopterin synthesis in the cell.
4	GCHFR	UNIPROT:P30047	inhibits		GO:0009058	Phenotype	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Cells overexpressing GFRP demonstrated significantly low biopterin levels after 48 h transfection, indicating that GFRP decreases biopterin synthesis in the cells.
4	GCHFR	UNIPROT:P30047	activates		MESH:D001708	Phenotype	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Together these results indicate that stimulation of biopterin synthesis by LPS involves signaling of GFRP, which by releasing GTPCH-I from allosteric inhibition increases biopterin synthesis in the cell.
4		UNIPROT:P04040	decreases	GCHFR	UNIPROT:P30047	Protein	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	In addition, control experiments showed that catalase reduces GFRP mRNA levels induced by GO, indicating the involvement of hydrogen peroxide in these responses (Fig. 5B).
4		PF:PF13146	activates	GCHFR	UNIPROT:P30047	ProteinFamily	af8bdde8-1c09-11f0-b759-0050569a791b	10.1016/j.jclepro.2024.140906	This section describes the environmental performance of the thermoset bio-based UPR developed in (Hofmann et al., 2022a) and of the corresponding bio-based GFRP composite (Hofmann et al., 2022b) produced by vacuum infusion (TRL 7).
4		MESH:D008070	decreases	GCHFR	UNIPROT:P30047	Phenotype	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	5A, LPS (50 μg/ml) treatment decreased GFRP mRNA levels in HAECs by approximately 80%.
4		UNIPROT:Q5T7V8	increases	GCHFR	UNIPROT:P30047	Protein	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	In addition, control experiments showed that catalase reduces GFRP mRNA levels induced by GO, indicating the involvement of hydrogen peroxide in these responses (Fig. 5B).
3	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	6fb48066-c47b-11e5-9cc6-001a4ae51246	PMC4677475	In vitro, GFRP inhibits GTPCH-1 activity in the presence of BH4by forming a complex with GTPCH-1.|||This diminishes the Vmaxof GTPCH-1, as shown by our own laboratory and others.2,3Crystal structures of the GTPCH-1/GFRP complex have shown that BH4is bound at the interface of these two proteins.4We have recently demonstrated that endogenous GFRP inhibits GTPCH-1 activity, thereby limiting BH4levels and NO production in human endothelial cells.3We therefore speculate that measures that cause dissociation of GTPCH-1 and GFRP would increase GTPCH-1 activity and ultimately BH4production.|||Agents that disrupt the binding of GTPCH-1 and GFRP might therefore have therapeutic potential because they would reduce GFRP inhibition of GTPCH-1 and enhance intracellular BH4production.
3	GCHFR	UNIPROT:P30047	inhibits		MESH:D009569	Phenotype	efa1c33e-3847-11e6-b56c-001a4ae51246	PMC4851220	We have previously shown that GFRP overexpression attenuates the increase in BH4and NO arising in response to a proinflammatory stimulusin vitro(20).|||We hypothesized that overexpression of GFRP would maintain the sensitivity of GCH1 to feedback inhibition, limit BH4bioavailability, and reduce pathological NO production, in a clinically relevant model of septic shock in which NO production is increased (32,33).|||In support of this, we have previously demonstrated,in vitro, that endothelial GFRP overexpression significantly reduces BH4and NO generation following proinflammatory stimulation but has no effect on BH4or NO accumulation under naive conditions (20).
3		UNIPROT:Q9LF80	increases	GCHFR	UNIPROT:P30047	Protein	e109004a-bc3b-11e5-8abe-001a4ae51246	PMC3023840	The fact that statin treatment influenced GFRP protein levels and GFRP protein binding in a similar way to GT3 and that mevalonate coadministration reversed the effects of both GT3 and statin strongly indicates that GT3 modulates GFRP levels and GFRP–GTPCH protein binding through inhibition of HMG-CoA reductase.|||On the other hand, GT3 induces a reduction in GFRP protein levels by reducing GFRP gene transcription.
3		UNIPROT:P01579	decreases	GCHFR	UNIPROT:P30047	Protein	e3775ce8-ca5d-11e5-a3f7-001a4ae51246	14514683	IFN-γ thus has a unique regulatory effect on PMC that potentiates BH4production through increased CHI and inhibiting GFRP expression.|||IFN-γ also decreases GFRP mRNA levels.
3		UNIPROT:Q13363	inhibits	GCHFR	UNIPROT:P30047	Protein	9cd127da-ae93-11ec-8f68-0050569a1f61	PMCPMC8125636	By reducing the GFRP tie spacing from 150 mm to 75 mm, a rise of 3.65% was detected for GGRAC compressive members with eight longitudinal bars.|||Similarly, by reducing the GFRP tie spacing from 150 mm to 75 mm, a rise of 7.37% was detected for GGRAC compressive members with ten longitudinal bars.|||By reducing the GFRP tie spacing from 150 mm to 75 mm, a rise of 7.99% was observed for GGRAC compressive members with six longitudinal bars.
2	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	0c44a8ea-d948-11ee-b346-0050569a791b	10.1016/j.jccr.2005.11.002	In addition to direct gene delivery of GTPCH I to improve its enzymatic capacity, activity of GTPCH I may also be negatively regulated by the GTPCH feedback regulatory protein (GFRP)[21,22], which forms a GFRP/GTPCH I complex to inhibit the activity of GTPCH I[23].
2	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	fbb3bec0-374b-11e8-8f56-001a4a160175	22770721	Recently, McHugh and colleagues reported that GTP-cyclohydrolase I feedback regulator (GFRP) gene, which mediates feedback inhibition of GCH1 activity by BH4, was associated with the serotonin selective reuptake inhibitors (SSRIs), which are antidepressant, response in MDD patients in the New Zealand population (McHugh et al., 2011).
2	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	Parallel to the strong induction of GTP cyclohydrolase I, GFRP mRNA is down-regulated.
2	GCHFR	UNIPROT:P30047	inhibits		PF:PF02180	ProteinFamily	285158cc-cb2c-11e5-8189-001a4ae51246	12359727	It has been shown that GTPCHI interacts with GFRP in the presence of BH4and GTP, resulting in the formation of an inhibitory protein complex, which suppressesde novosynthesis of BH4(15,31).
2	GCHFR	UNIPROT:P30047	activates		UNIPROT:P30793	Protein	77c48022-ae93-11ec-840e-0050569a791b	PMCPMC8429800	In the presence of phenylalanine, GFRP interacts with GCH1 to activate the GCH1 activity (42, 43).|||The mRNA expressions of GFRP in lung and liver of wild- type mice increase after 8.5 Gy of total body Irradiation (TBI), suggesting that the inhibition of GCH1 activity mediated by GFRP may be a possible mechanism of BH4 inhibition after ionizing irradiation (54, 57).
2	GCHFR	UNIPROT:P30047	increases		PF:PF02180	ProteinFamily	6ecbe2f6-c472-11e5-8491-001a4ae51247	PMC2679467	These results indicate that GFRP could also be involved in oxidant signaling pathways where up-regulation of GFRP could inhibit GTPCH activity and thus reduce BH4 levels.|||This experiment will provide evidence of whether the absence of GFRP would induce prominent changes in BH4 levels through changes in GTPCH activity.
2		CHEBI:16240	activates	GCHFR	UNIPROT:P30047	Chemical	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Hydrogen peroxide augments GFRP mRNA and GTPCH-I in endothelial cells Low BH4levels appear to be a trait of vascular dysfunction[33–36].
2		UNIPROT:P60880	decreases	GCHFR	UNIPROT:P30047	Protein	285158cc-cb2c-11e5-8189-001a4ae51246	12359727	Indeed, Western blot analysis showed that SNAP pretreatment suppressed the GFRP level.
2		MESH:D009569	increases	GCHFR	UNIPROT:P30047	Phenotype	285158cc-cb2c-11e5-8189-001a4ae51246	12359727	This suggests that the suppression of GFRP expression by NO is a mechanism to amplify NO production and protect hepatocytes from injury during acute inflammatory states.
2		MESH:D011622	increases	GCHFR	UNIPROT:P30047	Phenotype	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	Thus, either low levels of GFRP still mediated feedback inhibition by pterins but can no longer mediate phenylalanine effects, or yet unknown proteins different from GFRP may be responsible for this effect.
2		MESH:D008070	increases	GCHFR	UNIPROT:P30047	Phenotype	312daf22-bc40-11e5-8d2d-001a4ae51247	10.1016/j.freeradbiomed.2004.11.004	Thus, it appears that LPS stimulates both an increase in GTPCH-I expression and a diminution in GFRP levels.
2		UNIPROT:P01579	inhibits	GCHFR	UNIPROT:P30047	Protein	e3775ce8-ca5d-11e5-a3f7-001a4ae51246	14514683	IFN-γ significantly down-regulates GFRP mRNA production in PMC, which coincides with increased CHI production.
2		UNIPROT:Q9LF80	decreases	GCHFR	UNIPROT:P30047	Protein	e109004a-bc3b-11e5-8abe-001a4ae51246	PMC3023840	Nuclear run-on assays showed that GT3 reduced GFRP expression by causing a reduction in GFRP gene transcription (p= 0.0008) (Fig. 5B).|||On the other hand, GT3 induces a reduction in GFRP protein levels by reducing GFRP gene transcription.
1	GCHFR	UNIPROT:P30047	activates		UNIPROT:P30793	Protein	f9c423d8-ca5c-11e5-8050-001a4ae51246	12734191	Notably, feedback inhibition results from BH4-induced complex formation of GTPCH with a regulatory protein known as GTPCH feedback regulatory protein (GFRP) (4–6).
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	66a11110-c6b1-11ee-8b99-0050569a1f61	10.1016/j.gene.2023.147749	GFRP positively and negatively regulates the activity of GCH1 by forming heteromeric protein complex with GCH1.
1	GCHFR	UNIPROT:P30047	phosphorylatesProtein		UNIPROT:P30793	Protein	f56c1836-c485-11e5-9da3-001a4ae51247	23104880	Using small interfering RNA or overexpressing plasmids, GFRP was shown to modulate phosphorylation of GTPCH-1, BH4 levels, and NO production in human endothelial cells.
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	1029bdf8-cb2b-11e5-9aa0-001a4ae51247	PMC122169	"Phenylalanine and GFRP reduce the positive cooperativity of GTPCHI and, as a result, stimulate the enzyme's activity in
                            the presence of subsaturating concentrations of GTP."
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	9153694c-3809-11e6-8a17-001a4ae51247	PMC4470720	GFRP inhibits GCH1 by a direct binding mechanism that requires BH4 at the interface between the two proteins (43).
1	GCHFR	UNIPROT:P30047	dephosphorylatesProtein		UNIPROT:P30793	Protein	87094226-351f-11e8-b868-001a4a160176	23634439	Interestingly, a recent study by the same group demonstrated siRNA mediated knockdown GFRP enhanced GCH1 phosphorylation and that laminar shear caused in a disassociation between GFRP and GCH1 (Li et al., n.a.
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	8006e3d6-c463-11e5-91a7-001a4ae51247	PMC4665563	Recent studies have shown GFRP expression was increased at the mRNA level in lung and liver tissue samples of wild-type mice after 8.5 Gy of TBI, indicating a GFRP-mediated inhibition of GTPCH1 activity as a possible mechanism of BH4 suppression after IR exposure [35,51].
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	1a63e92e-c478-11e5-9da3-001a4ae51247	PMC3077585	Thus, when cellular BH4levels are sufficient, GFRP binds to and inhibits GTPCH-1 function in a negative feedback fashion.
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:P30793	Protein	3711e672-bc38-11e5-ac4e-001a4ae51246	PMC3313957	GFRP specifically binds to GCH1 and mediates BH4 feedback inhibition and phenylalanine feed-forward stimulation of GCH1 activity[13],[14].
1	GCHFR	UNIPROT:P30047	activates		UNIPROT:Q12841	Protein	d4f84322-ae94-11ec-8f68-0050569a1f61	PMCPMC8839721	In this paper, waste glass FRP (GFRP) bars were cut into particles of 12 sizes to enable the grading of recycled FRP aggregate (RFA) as similar as possible to that of NAC.
1	GCHFR	UNIPROT:P30047	inhibits		UNIPROT:Q13867	Protein	b1e2d6cc-7f6f-11ea-8187-001a4a160175	PMC7119135	Overexpression of GFRP reduces basal BH 4 levels (26) and attenuates the rise in BH 4 and NO that occurs in response to a proinflammatory stimulus (27) .
1	GCHFR	UNIPROT:P30047	activates		CHEBI:16240	Chemical	6ecbe2f6-c472-11e5-8491-001a4ae51247	PMC2679467	In addition to allosteric regulation by phenylalanine or BH4, recent studies have suggested that altered expression of GFRP might also contribute to changes in GTPCH activity and BH4 levels, in response to proinflammatory stimuli and hydrogen peroxide (6–9).
1	GCHFR	UNIPROT:P30047	inhibits		CHEBI:27601	Chemical	3d40246a-3408-11e8-8f56-001a4a160175	23085509	In conjunction with the stimulatory effect of IFN-γ on the expression of GCH, GFRP inhibition further upregulates the production of pteridine derivatives neopterin in human monocytic cells and BH4in other cells.
1	GCHFR	UNIPROT:P30047	inhibits		CHEBI:136604	Chemical	e3775ce8-ca5d-11e5-a3f7-001a4ae51246	14514683	CHI activity is regulated at multiple levels, including transcription and phosphorylation, and can be inhibited by the CHI feedback regulatory protein (GFRP) (5,6).
1	GCHFR	UNIPROT:P30047	activates		GO:0009058	Phenotype	8006e3d6-c463-11e5-91a7-001a4ae51247	PMC4665563	The expression of GFRP can be expected to inversely modulate BH4 biosynthesis.
1	GCHFR	UNIPROT:P30047	inhibits		MESH:D009569	Phenotype	f56c1836-c485-11e5-9da3-001a4ae51247	23104880	We also found that both GTPCH-1 phosphorylation and GFRP downregulation prevents endothelial NO synthase uncoupling in response to oscillatory shear.
1	GCHFR	UNIPROT:P30047	activates		MESH:D009569	Phenotype	b1e2d6cc-7f6f-11ea-8187-001a4a160175	PMC7119135	Overexpression of GFRP reduces basal BH 4 levels (26) and attenuates the rise in BH 4 and NO that occurs in response to a proinflammatory stimulus (27) .
1	GCHFR	UNIPROT:P30047	phosphorylatesProtein		MESH:D009569	Phenotype	f56c1836-c485-11e5-9da3-001a4ae51247	23104880	Using small interfering RNA or overexpressing plasmids, GFRP was shown to modulate phosphorylation of GTPCH-1, BH4 levels, and NO production in human endothelial cells.
1	GCHFR	UNIPROT:P30047	activates		MESH:D012772	Phenotype	efa1c33e-3847-11e6-b56c-001a4ae51246	PMC4851220	We hypothesized that overexpression of GFRP would maintain the sensitivity of GCH1 to feedback inhibition, limit BH4bioavailability, and reduce pathological NO production, in a clinically relevant model of septic shock in which NO production is increased (32,33).
1	GCHFR	UNIPROT:P30047	activates		GO:0009765	Phenotype	8c351615-5179-11eb-88fd-001a4a160176	PMC7796393	This may be one of the reasons of observing lower value of acceleration in SMA/GFRP specimens, which in turn could lead to higher energy dissipation by vibration in SMA/GFRP specimens.
1	GCHFR	UNIPROT:P30047	activates		MESH:D051379	Phenotype	8006e3d6-c463-11e5-91a7-001a4ae51247	PMC4665563	Our data demonstrated that when exposed to a non-lethal dose of IR, Gfrp overexpressing mice exhibited a significant accumulation of metabolites associated with oxidative stress and lipid peroxidation.
1	GCHFR	UNIPROT:P30047	inhibits		GO:0006915	Phenotype	a44bfd6e-ab29-11e6-8237-001a4ae51246	PMC5444681	GT3 also ameliorated endothelial cell apoptosis, reduced endothelial cell guanosine triphosphate cyclohydrolase 1 (GTPCH) feedback regulatory protein (GFRP) levels and GFRP-GTPCH binding by decreasing transcription of the GFRP gene.
1	GCHFR	UNIPROT:P30047	inhibits		MESH:D019798	Phenotype	3d40246a-3408-11e8-8f56-001a4a160175	23085509	In conjunction with the stimulatory effect of IFN-γ on the expression of GCH, GFRP inhibition further upregulates the production of pteridine derivatives neopterin in human monocytic cells and BH4in other cells.
1	GCHFR	UNIPROT:P30047	activates		GO:0006729	Phenotype	d078cb72-cb2a-11e5-b419-001a4ae51246	11799107	In the present work we investigated the role of GFRP in cytokine-induced tetrahydrobiopterin biosynthesis.
1	GCHFR	UNIPROT:P30047	activates		GO:0032615	Phenotype	6e145844-cb29-11e5-a6cd-001a4ae51247	11679675	These include proapoptotic genes that may lead to early death of infected cells (16) as well as genes encoding mcp-1, which can block IL-12 production in macrophages (20); HLA-E, which can inhibit natural killer cells (21); Gfrp, a close homolog of a protein that inhibits NO synthesis (22); and IDO, which can inhibit T cell activation (23).
1	GCHFR	UNIPROT:P30047	inhibits		FPLX:Notch	ProteinFamily	c8bbbbb8-85af-11ee-9458-0050569a1f61	10.1007/s00107-022-01822-6	Unlike the traditional wood screws, the GFRP reinforcement bond with the beams was strong enough to prevent premature notch failure.
1	GCHFR	UNIPROT:P30047	increases		PF:PF01342	ProteinFamily	544f80a2-cbf0-11ee-b346-0050569a791b	10.1016/j.resconrec.2013.10.001	In compression, loading capacity of PMs increases with increasing replacement amounts of sand aggregates by GFRP recyclates up to 8% in waste weight content.
1	GCHFR	UNIPROT:P30047	activates		PF:PF02180	ProteinFamily	8006e3d6-c463-11e5-91a7-001a4ae51247	PMC4665563	The expression of GFRP can be expected to inversely modulate BH4 biosynthesis.
1	GCHFR	UNIPROT:P30047	phosphorylatesProtein		PF:PF02180	ProteinFamily	f56c1836-c485-11e5-9da3-001a4ae51247	23104880	Using small interfering RNA or overexpressing plasmids, GFRP was shown to modulate phosphorylation of GTPCH-1, BH4 levels, and NO production in human endothelial cells.
1	GCHFR	UNIPROT:P30047	increases		PF:PF02180	ProteinFamily	f56c1836-c485-11e5-9da3-001a4ae51247	23104880	Using small interfering RNA or overexpressing plasmids, GFRP was shown to modulate phosphorylation of GTPCH-1, BH4 levels, and NO production in human endothelial cells.
1	GCHFR	UNIPROT:P30047	inhibits		PF:PF02180	ProteinFamily	3711e672-bc38-11e5-ac4e-001a4ae51246	PMC3313957	GFRP specifically binds to GCH1 and mediates BH4 feedback inhibition and phenylalanine feed-forward stimulation of GCH1 activity[13],[14].
1	GCHFR	UNIPROT:P30047	inhibits		PF:PF02180	ProteinFamily	0d125a32-bc2e-11e5-9b9d-001a4ae51247	PMC4053308	"On the basis of these results, it
 may be reasonable to assume that radiation causes an increase in Gfrp
 expression, which is expected to suppress BH4 bioavailability, resulting
 in higher oxidative stress in control Gfrp mice."
1		MESH:D005978	inhibits	GCHFR	UNIPROT:P30047	Phenotype	0d125a32-bc2e-11e5-9b9d-001a4ae51247	PMC4053308	"On the other hand, at 24 h following IR, total
 GSH levels were significantly decreased (more than 60%) in Gfrp knock-in
 mouse livers, resulting in a 1.8 fold increase in % GSSG compared
 to sham-irradiated Gfrp transgenic mice."
1		UNIPROT:P30793	inhibits	GCHFR	UNIPROT:P30047	Protein	efa1c33e-3847-11e6-b56c-001a4ae51246	PMC4851220	Interestingly, mammals already have an endogenous method of reversibly controlling BH4bioavailability: GCH1 activity can be directly inhibited by BH4, but only when GCH1 is complexed with its regulatory protein GFRP (GCH1 feedback regulatory protein) (16).
1		UNIPROT:P30793	activates	GCHFR	UNIPROT:P30047	Protein	3711e672-bc38-11e5-ac4e-001a4ae51246	PMC3313957	In endothelial cells, laminar shear stress causes dissociation of GCH1 and GFRP probably by increasing GCH1 phosphorylation[16].
1		MESH:D006863	activates	GCHFR	UNIPROT:P30047	Phenotype	76b3a834-ae93-11ec-840e-0050569a791b	PMCPMC8469038	In contrast, the MB solution containing the oxidatively fired GFRP/clay ceramic sample was alkaline, and the pH value increased with the GFRP mixing ratio because of the glass fibers, which mainly comprised calcium.
1		UNIPROT:P31944	activates	GCHFR	UNIPROT:P30047	Protein	efa1c33e-3847-11e6-b56c-001a4ae51246	PMC4851220	Mice overexpressing GFRP were developed in collaboration with Nucleis (France).
1		UNIPROT:Q9LF80	inhibits	GCHFR	UNIPROT:P30047	Protein	e109004a-bc3b-11e5-8abe-001a4ae51246	PMC3023840	Further research is needed to determine whether GT3 can prevent the postirradiation decline in BH4 availability by suppressing GFRP productionin vivo.
1		UNIPROT:Q9LF80	increases	GCHFR	UNIPROT:P30047	Protein	66c93cce-15e5-11e6-ae18-001a4ae51246	PMC4881489	GT3 may produce some of its valuable effects on free radical production after irradiation partly by offsetting the reduction in BH4, potentially by reducing the expression of GFRP.
1		UNIPROT:Q9LF80	inhibits	GCHFR	UNIPROT:P30047	Protein	66c93cce-15e5-11e6-ae18-001a4ae51246	PMC4881489	GT3 administration modulated apoptosis of endothelial cells, reduced guanosine triphosphate cyclohydrolase-1 (GTPCH) feedback regulatory protein, known as GFRP, and resulted in reduced GFRP-GTPCH binding.
1		MESH:D006160	activates	GCHFR	UNIPROT:P30047	Phenotype	b486eee2-f540-11eb-ae65-001a4a160175	29740802	GTP cyclohydrolase mediates the feedback inhibition I feedback regulatory protein (GFRP); defects affecting GFRP activity can cause hyperphenylalaninemia and neurological disorders [19].
1		PF:PF02180	increases	GCHFR	UNIPROT:P30047	ProteinFamily	7cb191da-ea3a-11ee-9aaa-0050569a1f61	10.1016/j.bbi.2022.06.016	It has been previously described that BH4 administration at our dose induced a reduction in GFRP mRNA expression in the brain of hyperphenylalaninemic ENU1/2 mice (Scherer et al., 2018).
1		PF:PF02180	activates	GCHFR	UNIPROT:P30047	ProteinFamily	0e0103ec-c9ff-11e5-ab20-001a4ae51246	15448133	Gel filtration experiments have suggested that the resulting BH4-induced inhibitory or phenylalanine-induced stimulatory complex contains two GFRP pentamers and one GTPCHI decamer (14-16).
1		PF:PF02180	inhibits	GCHFR	UNIPROT:P30047	ProteinFamily	029d3f08-c9fe-11e5-ab20-001a4ae51246	15292175	"Notably, no detectable reversal of GTPCH inhibition was found with other aromatic amino acids, Tyr, or Trp at concentrations
                      up to 6 mm.2Similarly, BH4-mediated GFRP-dependent inhibition of GTPCH has been found to be reversed byl-Phe and by no other naturally occurring amino acids (35,36)."
1		MESH:D051379	activates	GCHFR	UNIPROT:P30047	Phenotype	8006e3d6-c463-11e5-91a7-001a4ae51247	PMC4665563	We applied a combination of untargeted and targeted quantitative mass spectrometry to study the changes in IR-induced liver injury in mice overexpressing Gfrp, which resulted in decreased levels of BH4 as we previously discussed in this review.
1		MESH:D051379	activates	GCHFR	UNIPROT:P30047	Phenotype	77c48022-ae93-11ec-840e-0050569a791b	PMCPMC8429800	Cheema et al. investigated liver metabolic changes following irradiation in control and GFRP overexpression mice (57).
1		MESH:D051379	activates	GCHFR	UNIPROT:P30047	Phenotype	0d125a32-bc2e-11e5-9b9d-001a4ae51247	PMC4053308	"Taken together, our
 data demonstrate that Gfrp overexpressing mice exhibit higher susceptibility
 to a compromised liver function in response to radiation exposure."
1		MESH:D051379	activates	GCHFR	UNIPROT:P30047	Phenotype	efa1c33e-3847-11e6-b56c-001a4ae51246	PMC4851220	BH4levels changed during sepsis progression in WT mice, rising significantly at 6 h and returning to baseline by 24 h, whereas mice overexpressing GFRP did not display this transient increase in BH4(Fig.4, A and B).
1		UNIPROT:P01375	decreases	GCHFR	UNIPROT:P30047	Protein	3d40246a-3408-11e8-8f56-001a4a160175	23085509	Likewise, in untreated human umbilical vein endothelial cells (HUVEC), TNF-α and IFN-γ decrease the expression of GFRP mRNA by 90% (Shiraishi et al., 2011).
1		UNIPROT:P01579	decreases	GCHFR	UNIPROT:P30047	Protein	3d40246a-3408-11e8-8f56-001a4a160175	23085509	Likewise, in untreated human umbilical vein endothelial cells (HUVEC), TNF-α and IFN-γ decrease the expression of GFRP mRNA by 90% (Shiraishi et al., 2011).
1		UNIPROT:P00846	activates	GCHFR	UNIPROT:P30047	Protein	158d731c-c851-11ee-9133-0050569a1f61	10.1016/j.wasman.2023.03.041	RP allows the recovery of GFRP as-is by segmenting the WT blades (Huysmann et al., 2017).
1		PUBCHEM:252	inhibits	GCHFR	UNIPROT:P30047	Chemical	0e0103ec-c9ff-11e5-ab20-001a4ae51246	15448133	8 Å crystal structure of the BH2-induced inhibitory complex of rat GTPCHI and GFRP.
1		CHEBI:87631	increases	GCHFR	UNIPROT:P30047	Chemical	e109004a-bc3b-11e5-8abe-001a4ae51246	PMC3023840	The fact that statin treatment influenced GFRP protein levels and GFRP protein binding in a similar way to GT3 and that mevalonate coadministration reversed the effects of both GT3 and statin strongly indicates that GT3 modulates GFRP levels and GFRP–GTPCH protein binding through inhibition of HMG-CoA reductase.
1		UNIPROT:P06956	activates	GCHFR	UNIPROT:P30047	Protein	efa1c33e-3847-11e6-b56c-001a4ae51246	PMC4851220	We validated the specificity and efficiency of Cre-mediated recombination by crossing dormant GFRP transgenic mice with Cre recombinase mice under the control of an αSM-Cre promoter and subsequently characterized the cardiovascular and metabolic phenotype under naive and septic conditions.