Property Summary

NCBI Gene PubMed Count 61
PubMed Score 105.70
PubTator Score 88.33

Knowledge Summary


No data available



Accession P46695 Q5SU30 Q92691 Q93044
Symbols DIF2


  Ortholog (1)

Species Source Disease
Chimp OMA Inparanoid

Protein-protein Interaction (4)

Gene RIF (41)

25684507 High expression of IER3 is associated with hepatocarcinoma.
25666857 findings suggest that IER3 is a putative tumor suppressor in the cervix, and the c-Ab1/p73beta/IER3 axis is a novel and crucial signaling pathway that confers etoposide chemosensitivity.
25066273 interleukin-1beta (IL-1beta)-induced IER3 expression is mediated by the ERK1/2 target, transcription factor Elk-1.
25036043 In human samples removed from failed AVF, there was a significant increase in IEX-1 expression localized to the adventitia.
24311782 the interference of IER3 with the PI3K/Akt-Fyn pathway represents a novel mechanism of Nrf2 regulation that may get lost in tumors and by which IER3 exerts its stress-adaptive and tumor-suppressive activity.
24162774 HIV-1 gp120 upregulates the expression of immediate early response 3 (IER3) in human B cells
23725081 IEX-1 expression levels correlate with the severity of preeclampsia
23403649 Studied the binding effect of hcmv-miR-UL148D to the 3' untranslated region (3'UTR) of IEX-1.Results showed that only one binding site in the 3'UTR of IEX-1 was completely complementary to an 11nt sequence in the 5' terminus of hcmv-mir-UL148D.
22085302 Altered IEX-1 expression can potentially be a new predictor of the malignant transformation and a prognostic indicator for cancer therapy.
21518511 Changes of methylation status of gene IEX-1 promoter CpG island correlates with hematologic malignancies.
21250941 IEX-1 plays a role in suppression of apoptosis and protects cells by controlling sensitivity to TNFalpha under both normal and inflammatory conditions.
21112119 IER3 plays a complex and to some extent contradictory role in cell cycle control and apoptosis. Effects of IER3 relate to an interference with certain signalling pathways
20934684 IER3 is upregulated in human PDLCs subjected to tensile stress related to mechano-induced cell cycle arrest.
20713914 Results suggest that hypertension in IEX-1 knockout mice may arise primarily from impaired cAMP signaling induced by overproduction of mitochondrial reactive oxygen species in vascular smooth muscle cells.
20587610 Observational study of gene-disease association. (HuGE Navigator)
19851445 Observational study of gene-disease association. (HuGE Navigator)
19837266 Observational study of gene-disease association. (HuGE Navigator)
19773435 Results suggest dysregulated expression of IER3 is common in MDS (61% >4-fold increase or decrease in expression with decreased expression primarily in early MDS and increased expression primarily in later MDS progressing toward leukemia).
19690192 The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype
19285955 This study demonstrated the physical association of the MCL-1 and IEX-1 proteins, the modulatory role of MCL-1 in IEX-1-induced apoptosis, and the role of BIM as an essential downstream molecule for IEX-1-induced cell death.
19152102 down-regulation of IEX-1 gene was associated with short survival in myelodysplastic syndrome patients
18564103 study showed that IEX-1 is involved in the radiation-induced apoptosis of human glioma cells and that its overexpression enhances the apoptotic sensitivity of these cells to gamma-radiation
18026799 This study indicates that an evaulation of IEX-1 expression may be clinically useful for predicting patient prognosis in pancreatic cancer.
17704804 Modulates NF-kappaB-dependent antiapoptotic protection and thereby exerts tumor-suppressive potential.
16973576 ICP27 is essential for IEX-1 mRNA stabilization whereas virion host shut plays little if any role
16960879 IEX-1 plays an important role in astrocytic differentiation of human glioma cells and that IEX-1 functions at downstream of PKA.
16567805 sequence-targeting mutagenesis reveals a transmembrane-like integrated region of the protein that is critical for both pro-apoptotic and anti-apoptotic functions
15855159 IEX-1 is organized in subnuclear structures and partially co-localizes with promyelocytic leukemia protein in HeLa cells
15781630 We found that p73beta targets the apoptotic program at multiple levels: facilitating caspase activation through p53-dependent signals and inducing p57KIP2, while down-regulating c-IPA1 and IEX1 through a p53-independent mechanism.
15767410 concluded that IEX-1 mRNA is not preferentially degraded during HSV-1 infection and that HSV-1 instead inhibits the normal turnover of this mRNA
15451437 Our data suggest that IEX-1 may regulate apoptosis by directly interacting with various proteins involved in the control of apoptotic pathways.
15120418 IEX-1 expression was stimulated by hydroxytamoxifen, that the degree of increase was greater in resistant cells (four-fold versus 1.5-fold) and that this hydroxytamoxifen regulation was estrogen receptor dependent
12761504 IEX-1 attenuates NF-kappaB activation, a possible counter-regulatory process leading to apoptosis.
12743274 failure of IEX-1 to express its protein reflects the numerous mechanisms by which HSV-1 thwarts the cells from expressing its genes after infection
12682234 Overexpression of IEX-1S results in acceleration of TNF-alpha-induced hepatocyte apoptosis through blockade of the PI3K/Akt survival pathway.
12510147 IEX-1 has roles in regulation of cell death and oncogenesis [review]
12356731 IEX-1 is a new type of ERK substrate that has a dual role in ERK signaling by acting both as an ERK downstream effector mediating survival and as a regulator of ERK activation
12032839 Characterization of a novel hexameric repeat DNA sequence in the promoter of the immediate early gene, IEX-1, that mediates 1alpha,25-dihydroxyvitamin D(3)-associated IEX-1 gene repression.
11910304 mechanical strain increased IEX-1 gene expression in macrophages
11844788 regulation by p53 tumor suppressor and Sp1
11782530 Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice.

AA Sequence

YALDLSTFLQQHPAAF                                                          141 - 156

Text Mined References (64)

PMID Year Title
25684507 2015 Expression of IER3 in primary hepatocarcinoma: correlation with clinicopathological parameters.
25666857 2015 IER3 is a crucial mediator of TAp73?-induced apoptosis in cervical cancer and confers etoposide sensitivity.
25066273 2014 Transcription factor Elk-1 participates in the interleukin-1?-dependent regulation of expression of immediate early response gene 3 (IER3).
25036043 2014 The role of Iex-1 in the pathogenesis of venous neointimal hyperplasia associated with hemodialysis arteriovenous fistula.
24311782 2014 Modulation of nuclear factor E2-related factor-2 (Nrf2) activation by the stress response gene immediate early response-3 (IER3) in colonic epithelial cells: a novel mechanism of cellular adaption to inflammatory stress.
23725081 2013 The expression of immediate early response gene X-1 in preeclampsia placenta and its pro-apoptotic role in preeclampsia.
23455636 2013 Seven new loci associated with age-related macular degeneration.
23403649 2013 Identification of immediate early gene X-1 as a cellular target gene of hcmv-mir-UL148D.
22565310 2012 Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis.
22085302 2011 Clinical significance of IEX-1 expression in ovarian carcinoma.
21518511 2011 [Methylation status of IEX-1 gene promotor CpG island in malignant hematopoietic cell lines].
21250941 2011 IEX-1 suppresses apoptotic damage in human intestinal epithelial Caco-2 cells induced by co-culturing with macrophage-like THP-1 cells.
21112119 Role of the immediate early response 3 (IER3) gene in cellular stress response, inflammation and tumorigenesis.
20934684 2011 Early proliferation alteration and differential gene expression in human periodontal ligament cells subjected to cyclic tensile stress.
20848476 2010 Genetic predictors of medically refractory ulcerative colitis.
20713914 2010 Impaired 3',5'-cyclic adenosine monophosphate-mediated signaling in immediate early responsive gene X-1-deficient vascular smooth muscle cells.
20587610 2010 Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection.
20467439 2010 ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response.
19851445 2009 High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions.
19837266 2009 TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility.
19773435 2009 Rearrangements and amplification of IER3 (IEX-1) represent a novel and recurrent molecular abnormality in myelodysplastic syndromes.
19690192 2009 Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
19285955 2009 IEX-1-induced cell death requires BIM and is modulated by MCL-1.
19152102 2009 Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18564103 2009 Overexpression of immediate early gene X-1 (IEX-1) enhances gamma-radiation-induced apoptosis of human glioma cell line, U87-MG.
18482256 2009 Protein microarray analysis identifies human cellular prion protein interactors.
18191642 2008 IEX-1 directly interferes with RelA/p65 dependent transactivation and regulation of apoptosis.
18026799 2008 Prognostic significance of the immediate early response gene X-1 (IEX-1) expression in pancreatic cancer.
17704804 2008 The apoptosis-inducing effect of gastrin on colorectal cancer cells relates to an increased IEX-1 expression mediating NF-kappa B inhibition.
16973576 2006 Herpes simplex virus ICP27 is required for virus-induced stabilization of the ARE-containing IEX-1 mRNA encoded by the human IER3 gene.
16960879 2007 Immediate early gene IEX-1 induces astrocytic differentiation of U87-MG human glioma cells.
16702430 2006 Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity.
16567805 2006 Distinct domains for anti- and pro-apoptotic activities of IEX-1.
16456541 2006 B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15855159 2005 Immediate early gene X1 (IEX-1) is organized in subnuclear structures and partially co-localizes with promyelocytic leukemia protein in HeLa cells.
15781630 2005 p73beta-Mediated apoptosis requires p57kip2 induction and IEX-1 inhibition.
15767410 2005 Herpes simplex virus infection stabilizes cellular IEX-1 mRNA.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15451437 2004 Immediate early gene X-1 interacts with proteins that modulate apoptosis.
15120418 2004 Immediate early gene X-1 (IEX-1), a hydroxytamoxifen regulated gene with increased stimulation in MCF-7 derived resistant breast cancer cells.
14574404 2003 The DNA sequence and analysis of human chromosome 6.
12761504 2003 The early response gene IEX-1 attenuates NF-kappaB activation in 293 cells, a possible counter-regulatory process leading to enhanced cell death.
12743274 2003 The stress-inducible immediate-early responsive gene IEX-1 is activated in cells infected with herpes simplex virus 1, but several viral mechanisms, including 3' degradation of its RNA, preclude expression of the gene.
12682234 2003 Expression of the NF-kappa B target gene X-ray-inducible immediate early response factor-1 short enhances TNF-alpha-induced hepatocyte apoptosis by inhibiting Akt activation.
12510147 2003 Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12356731 2002 IEX-1: a new ERK substrate involved in both ERK survival activity and ERK activation.
11910304 2002 Identification of mechanically induced genes in human monocytic cells by DNA microarrays.
11844788 2002 Divergent regulation of the growth-promoting gene IEX-1 by the p53 tumor suppressor and Sp1.
11782530 2002 Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice.
11455449 2001 Expression of an immediate early gene, IEX-1, in human tissues.
10448082 1999 The putative apoptosis inhibitor IEX-1L is a mutant nonspliced variant of p22(PRG1/IEX-1) and is not expressed in vivo.
9878538 1998 A novel immediate early response gene, IEX-1, is induced by ultraviolet radiation in human keratinocytes.
9828130 1998 Cloning of ARE-containing genes by AU-motif-directed display.
9791001 1998 Regulation of a novel immediate early response gene, IEX-1, in keratinocytes by 1alpha,25-dihydroxyvitamin D3.
9781666 1998 The promoter of human p22/PACAP response gene 1 (PRG1) contains functional binding sites for the p53 tumor suppressor and for NFkappaB.
9703517 1998 IEX-1L, an apoptosis inhibitor involved in NF-kappaB-mediated cell survival.
9588170 1998 Genomic organization, promoter cloning, and chromosomal localization of the Dif-2 gene.
9196025 1997 Identification and characterization of a novel monocyte/macrophage differentiation-dependent gene that is responsive to lipopolysaccharide, ceramide, and lysophosphatidylcholine.
8653710 1996 PRG1: a novel early-response gene transcriptionally induced by pituitary adenylate cyclase activating polypeptide in a pancreatic carcinoma cell line.
8603392 1996 Identification and characterization of a radiation-inducible glycosylated human early-response gene.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.