Ignet

Gene Information

Gene symbol: ERN1

Gene name: endoplasmic reticulum to nucleus signaling 1

HGNC ID: 3449

Synonyms: IRE1, IRE1P

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	ADIPOQ	1 hits
3	ALPK3	1 hits
4	ATF3	1 hits
5	ATF4	1 hits
6	ATF6	1 hits
7	ATP2C1	1 hits
8	BECN1	1 hits
9	DDIT3	1 hits
10	EIF2A	1 hits
11	EIF2AK2	1 hits
12	EIF2AK3	1 hits
13	EIF2S1	1 hits
14	FAS	1 hits
15	HCN2	1 hits
16	HRK	1 hits
17	HSPA5	1 hits
18	IGF1	1 hits
19	JUN	1 hits
20	MAPK8	1 hits
21	PDIA2	1 hits
22	PKLR	1 hits
23	PPP1R15A	1 hits
24	PRKAA1	1 hits
25	SCD	1 hits
26	TRIM3	1 hits
27	WFS1	1 hits
28	XBP1	1 hits

Related Sentences

#	PMID	Sentence
1	12101393	In mammals, ER stress transducer proteins IRE1, PERK and ATF6 activate both survival and apoptotic pathways.
2	12101393	The former includes transcriptional induction of ER chaperones, translational attenuation, and ER-associated degradation (ERAD) while the latter includes transcriptional induction of CHOP/GADD153, the activation of cJUN NH(2)-terminal kinase, and the activation of caspase-12.
3	15623514	A small interfering RNA causes knockdown of ATP2C1 expression, resulting in defects in both post-translational processing of wild-type thyroglobulin (a secretory glycoprotein) as well as endoplasmic reticulum-associated protein degradation of mutant thyroglobulin, whereas degradation of a nonglycosylated misfolded secretory protein substrate appears unaffected.
4	15623514	Knockdown of ATP2C1 is not associated with elevated steady state levels of ER chaperone proteins, nor does it block cellular activation of either the PERK, ATF6, or Ire1/XBP1 portions of the ER stress response.
5	16195229	The expression of WFS1 is regulated by inositol requiring 1 and PKR-like ER kinase, central regulators of the unfolded protein response.
6	16195229	WFS1 is normally up-regulated during insulin secretion, whereas inactivation of WFS1 in beta-cells causes ER stress and beta-cell dysfunction.
7	17158450	Salubrinal induced a marked eIF2alpha phosphorylation and potentiated the inhibitory effects of free fatty acids on protein synthesis and insulin release.
8	17158450	The synergistic activation of the PERK-eIF2alpha branch of the endoplasmic reticulum stress response, but not of the IRE1 and activating transcription factor-6 pathways, led to a marked induction of activating transcription factor-4 and the pro-apoptotic transcription factor CHOP.
9	17349291	UPR involves the activation of three transmembrane proteins of the ER : the PKR-like ER protein kinase (PERK), the activating transcription factor 6 (ATF6) and the inositol requiring enzyme 1 (IRE-1).
10	18437163	Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum.
11	18437163	Here we demonstrate that human MCF-7 breast cancer cells, as well as murine NIH/3T3 fibroblasts, are rescued from ER stress-initiated apoptosis by insulin-like growth factor-I (IGF-I).
12	18437163	IGF-I significantly augments the adaptive capacity of the ER by enhancing compensatory mechanisms such as the IRE1 alpha-, PERK- and ATF6-mediated arms of ER stress signalling.
13	18437163	During ER stress, IGF-I stimulates translational recovery and induces expression of the key molecular chaperone protein Grp78/BiP, thereby enhancing the folding capacity of the ER and promoting recovery from ER stress.
14	18437163	Application of signal transduction inhibitors of MEK (U1026), PI3K (LY294002 and wortmannin), JNK (SP600125), p38 (SB203580), protein kinases A and C (H-89 and staurosporine) and STAT3 (Stattic) does not prevent IGF-I-mediated protection from ER stress-induced apoptosis.
15	18544642	In vitro, palmitate, thapsigargin, and tunicamycin but not oleate induced endoplasmic reticulum stress in HepG2 cells, including increased transcripts CHOP, ERN1, GADD34, and PERK, and increased XBP1 splicing along with phosphorylation of eukaryotic initiation factor eIF2alpha, JNK1, and c-jun.
16	18644846	The eukaryotic translation factor 2-alpha kinase 3 (EIF2AK3; also known as PERK) and endoplasmic reticulum to nucleus signaling 1 (ERN1; also known as IRE1) pathways, but not the activating transcription factor (ATF6) pathway of the unfolded protein response, are activated in such lipotoxic beta-cells.
17	18644846	Inclusion of diazoxide during culture attenuated activation of the EIF2AK3 pathway but not the ERN1 pathway.
18	18644846	The eukaryotic translation factor 2-alpha kinase 3 (EIF2AK3; also known as PERK) and endoplasmic reticulum to nucleus signaling 1 (ERN1; also known as IRE1) pathways, but not the activating transcription factor (ATF6) pathway of the unfolded protein response, are activated in such lipotoxic beta-cells.
19	18644846	Inclusion of diazoxide during culture attenuated activation of the EIF2AK3 pathway but not the ERN1 pathway.
20	19057532	Low levels of adiponectin, a fat-derived hormone, are found to be correlated with coronary heart disease, type 2 diabetes, obesity, and insulin resistance.
21	19057532	Expression and phosphorylation of IRS-1, Akt, c-Jun, and c-Jun N terminal kinase (JNK) as well as markers of endoplasmic reticulum (ER) stress were evaluated using western blotting.
22	19057532	Ratios between phosphorylated c-Jun and c-Jun as well as phosphorylated IRS-1 and IRS-1 were increased in db/db mice, the effect of which was attenuated by adiponectin.
23	19057532	Levels of the phosphorylated ER stress makers PERK (Thr980), IRE-1, and eIF2alpha were significantly elevated in db/db mice compared with lean controls, although the effect was unaffected by adiponectin.
24	19057532	Collectively, our data suggest that adiponectin improves cardiomyocyte dysfunction in db/db diabetic obese mice through a mechanism possibly related to c-Jun and IRS-1.
25	19468685	The IRE1/XBP1 branch of the UPR is activated by high dietary carbohydrates and controls the expression of genes involved in fatty acid and cholesterol biosynthesis.
26	19468685	PERK mediated eIF2alpha phosphorylation is also required for the expression of lipogenic genes and the development of hepatic steatosis, likely by activating C/EBP and PPARgamma transcription factors.
27	20922715	The core of this response is a triad of stress-sensing proteins: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6.
28	20922715	All three regulate portions of the transcriptional unfolded protein response, while PERK also attenuates protein synthesis during ER stress and IRE1 interacts directly with the c-Jun amino-terminal kinase stress kinase pathway.
29	20922715	The core of this response is a triad of stress-sensing proteins: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6.
30	20922715	All three regulate portions of the transcriptional unfolded protein response, while PERK also attenuates protein synthesis during ER stress and IRE1 interacts directly with the c-Jun amino-terminal kinase stress kinase pathway.
31	21329805	In mammals, the UPR is transduced through three parallel signaling pathways originating at the ER-resident transmembrane protein kinase-endoribonucleases (RNase) IRE1, the protein kinase PERK, and a family of type II transmembrane transcription factors, whose most prominent member is ATF6α.
32	21329805	To monitor activation of the IRE1 branch, a Northern blotting protocol to monitor splicing of HAC1 mRNA in yeast and a reverse transcriptase-PCR assay for processing of the IRE1 RNase substrate XBP1 in mammalian cells are presented.
33	21329805	Activation of the PERK branch is monitored via phosphorylation of the translation initiation factor eIF2α, induction of CHOP at the mRNA and protein level, and induction of ATF4 at the protein level.
34	21329805	In mammals, the UPR is transduced through three parallel signaling pathways originating at the ER-resident transmembrane protein kinase-endoribonucleases (RNase) IRE1, the protein kinase PERK, and a family of type II transmembrane transcription factors, whose most prominent member is ATF6α.
35	21329805	To monitor activation of the IRE1 branch, a Northern blotting protocol to monitor splicing of HAC1 mRNA in yeast and a reverse transcriptase-PCR assay for processing of the IRE1 RNase substrate XBP1 in mammalian cells are presented.
36	21329805	Activation of the PERK branch is monitored via phosphorylation of the translation initiation factor eIF2α, induction of CHOP at the mRNA and protein level, and induction of ATF4 at the protein level.
37	21809331	In mammalian cells, UPR is a complex signaling program mediated by three ER transmembrane receptors: activating transcription factor 6 (ATF6), inositol requiring kinase 1 (IRE1) and double-stranded RNA-activated protein kinase (PKR)-like endoplasmic reticulum kinase (PERK).
38	21896783	IRE1-dependent activation of AMPK in response to nitric oxide.
39	21896783	The known AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of AMPK by nitric oxide.
40	21896783	Nitric oxide-induced AMPK phosphorylation and subsequent signaling to AMPK substrates, including Raptor, acetyl coenzyme A carboxylase, and PGC-1α, is attenuated in IRE1α-deficient cells.
41	21896783	The endoribonuclease activity of IRE1 appears to be required for AMPK activation in response to nitric oxide.
42	21896783	In addition to nitric oxide, stimulation of IRE1 endoribonuclease activity with the flavonol quercetin leads to IRE1-dependent AMPK activation.
43	21896783	These findings indicate that the RNase activity of IRE1 participates in AMPK activation and subsequent signaling through multiple AMPK-dependent pathways in response to nitrosative stress.
44	21896783	IRE1-dependent activation of AMPK in response to nitric oxide.
45	21896783	The known AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of AMPK by nitric oxide.
46	21896783	Nitric oxide-induced AMPK phosphorylation and subsequent signaling to AMPK substrates, including Raptor, acetyl coenzyme A carboxylase, and PGC-1α, is attenuated in IRE1α-deficient cells.
47	21896783	The endoribonuclease activity of IRE1 appears to be required for AMPK activation in response to nitric oxide.
48	21896783	In addition to nitric oxide, stimulation of IRE1 endoribonuclease activity with the flavonol quercetin leads to IRE1-dependent AMPK activation.
49	21896783	These findings indicate that the RNase activity of IRE1 participates in AMPK activation and subsequent signaling through multiple AMPK-dependent pathways in response to nitrosative stress.
50	21896783	IRE1-dependent activation of AMPK in response to nitric oxide.
51	21896783	The known AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of AMPK by nitric oxide.
52	21896783	Nitric oxide-induced AMPK phosphorylation and subsequent signaling to AMPK substrates, including Raptor, acetyl coenzyme A carboxylase, and PGC-1α, is attenuated in IRE1α-deficient cells.
53	21896783	The endoribonuclease activity of IRE1 appears to be required for AMPK activation in response to nitric oxide.
54	21896783	In addition to nitric oxide, stimulation of IRE1 endoribonuclease activity with the flavonol quercetin leads to IRE1-dependent AMPK activation.
55	21896783	These findings indicate that the RNase activity of IRE1 participates in AMPK activation and subsequent signaling through multiple AMPK-dependent pathways in response to nitrosative stress.
56	21896783	IRE1-dependent activation of AMPK in response to nitric oxide.
57	21896783	The known AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of AMPK by nitric oxide.
58	21896783	Nitric oxide-induced AMPK phosphorylation and subsequent signaling to AMPK substrates, including Raptor, acetyl coenzyme A carboxylase, and PGC-1α, is attenuated in IRE1α-deficient cells.
59	21896783	The endoribonuclease activity of IRE1 appears to be required for AMPK activation in response to nitric oxide.
60	21896783	In addition to nitric oxide, stimulation of IRE1 endoribonuclease activity with the flavonol quercetin leads to IRE1-dependent AMPK activation.
61	21896783	These findings indicate that the RNase activity of IRE1 participates in AMPK activation and subsequent signaling through multiple AMPK-dependent pathways in response to nitrosative stress.
62	22355328	Glucose intolerance (iAUC increased by ∼60%) and blunted insulin-stimulated hepatic Akt and GSK3β phosphorylation (∼40-60%) were found in both feeding conditions (p<0.01 vs Con, assessed after 1 week).
63	22355328	No impairment of mitochondrial function was found (oxidation capacity, expression of PGC1α, CPT1, respiratory complexes, enzymatic activity of citrate synthase & β-HAD).
64	22355328	Interestingly, associated with the upregulated lipogenic enzymes (ACC, FAS and SCD1), two (PERK/eIF2α and IRE1/XBP1) of three ER stress pathways were significantly activated in HFru-fed mice.
65	22446326	Binding of human BiP to the ER stress transducers IRE1 and PERK requires ATP.
66	22446326	Based on the results, we hypothesize that in contrast to its mode of binding ATF6 and unfolded proteins, BiP binds to IRE1 and PERK in a different manner.
67	22446326	Binding of human BiP to the ER stress transducers IRE1 and PERK requires ATP.
68	22446326	Based on the results, we hypothesize that in contrast to its mode of binding ATF6 and unfolded proteins, BiP binds to IRE1 and PERK in a different manner.
69	22773666	Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β-cell apoptosis.
70	22773666	By microarray analysis, we identified a palmitate-triggered ER stress gene expression signature and the induction of the BH3-only proteins death protein 5 (DP5) and p53-upregulated modulator of apoptosis (PUMA).
71	22773666	Knockdown of either protein reduced cytochrome c release, caspase-3 activation, and apoptosis in rat and human β-cells.
72	22773666	DP5 induction depends on inositol-requiring enzyme 1 (IRE1)-dependent c-Jun NH₂-terminal kinase and PKR-like ER kinase (PERK)-induced activating transcription factor (ATF3) binding to its promoter.
73	22773666	PUMA expression is also PERK/ATF3-dependent, through tribbles 3 (TRB3)-regulated AKT inhibition and FoxO3a activation.
74	22820500	Inflammatory molecules such as MCP-1, TNF-α, IL-1β and IL-8 are known to promote angiogenesis.
75	22820500	MCP-induced protein (MCPIP), originally discovered as a novel zinc finger protein induced by MCP-1, is also induced by other inflammatory agents.
76	22820500	The aim of this study was to bridge this gap and delineate the sequential processes involved in angiogenesis mediated via MCPIP. siRNA knockdown of MCPIP was used to determine whether different inflammatory agents, MCP-1, TNF-α, IL-1β and IL-8, mediate angiogenesis via MCPIP in human umbilical vein endothelial cells (HUVECs).
77	22820500	Endoplasmic reticulum (ER) stress was blocked by tauroursodeoxycholate or knockdown of ER stress signaling protein IRE-1 and autophagy was inhibited by the use of 3'methyl adenine, or LY 294002 or by specific knockdown of beclin1.
78	22820500	Tube formation induced by inflammatory agents, TNF-α, IL-1β, IL-8 and MCP-1 was inhibited by knockdown of MCPIP.
79	23132339	Two branches of the UPR, namely IRE1/XBP1s and PERK/ATF4/CHOP, mediate the UPR-induced sensitisation of pancreatic beta cells to the proinflammatory effects of cytokines.
80	23349482	Endoplasmic reticulum (ER) stress is suggested to cause hepatic insulin resistance by increasing de novo lipogenesis (DNL) and directly interfering with insulin signaling through the activation of the c-Jun N-terminal kinase (JNK) and IκB kinase (IKK) pathway.
81	23349482	Of note, both the IRE1/XBP1 and PERK/eIF2α arms of unfolded protein response (UPR) signaling were activated.
82	23349482	While retaining the elevated DNL (indicated by the upregulation of SREBP1c, ACC, FAS, and SCD1 and [3H]H2O incorporation into lipids), FB treatment markedly increased fatty acid oxidation (indicated by induction of ACOX1, p-ACC, β-HAD activity, and [14C]palmitate oxidation) and eliminated the accumulation of diacylglycerols (DAGs), which is known to have an impact on insulin signaling.
83	23349482	These findings suggest that lipid accumulation (mainly DAGs), rather than the activation of JNK or IKK, is pivotal for ER stress to cause hepatic insulin resistance.
84	23415873	Stimulation of human T cells with PHA or CD3/CD28 induced IL-2 mRNA expression and activated the endoplasmic reticulum (ER) stress response.
85	23415873	The treatment of T cells with curcumin induced the unfolded protein response (UPR) signaling pathway, initiated by the phosphorylation of PERK and IRE1.
86	23415873	Furthermore, curcumin increased the expression of the ER stress associated transcriptional factors XBP-1, cleaved p50ATF6α and C/EBP homologous protein (CHOP) in human CD4+ and Jurkat T cells.
87	23415873	In PHA-activated T cells, curcumin further enhanced PHA-induced CHOP expression and reduced the expression of the anti-apoptotic protein Bcl-2.
88	23527285	In the present study, we identified that the major endoplasmic reticulum stress (ERS) marker, Grp78 and ERS-induced apoptotic factor, CHOP, were time-dependently increased by exposure of β-TC3 cells to FFA.
89	23527285	The expression of ATF6 and the phosphorylation levels of PERK and IRE1, which trigger ERS signaling, markedly increased after FFA treatments.
90	23527285	We also found that FFA-induced ERS was mediated by the store-operated Ca(2+) entry through promoting the association of STIM1 and Orai1.
91	23527285	Moreover, calpain-2 was required for FFA-induced expression of CHOP and activation of caspase-12 and caspase-3, thus promoting cell apoptosis in β-TC3 cells.
92	23638076	Compared with healthy blood donors, diabetic patients showed a profound decrease in both NKG2D-positive NK cells (44% vs. 55.5%, P<0.01) and NKp46-positive cells (26% vs. 50%, P<0.01).
93	23638076	Furthermore, markers of the Unfolded Protein Response (UPR) BiP, PDI and sXBP1 mRNAs were significantly increased in NK cells from T2D patients (P<0.05, P<0.01, P<0.05, respectively), indicating that ER stress is activated in vivo through both PERK and IRE1 sensors.
94	23638076	These results demonstrate for the first time defects in NK cell-activating receptors NKG2D and NKp46 in T2D patients, and implicate the UPR pathway as a potential mechanism.
95	23833251	In islet grafts from diabetic mice, expression levels of many UPR genes of the IRE1/ATF6 pathways, which are important for adaptation to endoplasmic reticulum stress, were markedly reduced compared with that in islet grafts from control mice.