Atlas of Genetics and Cytogenetics in Oncology and Haematology

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IRF1 (interferon regulatory factor 1)

Written2008-01Patricia Palladinetti, Geoff Symonds, Alla Dolnikov
Children's Cancer Institute Australia for Medical Research, PO Box 81 (High St), Randwick, NSW 2031, Australia (PP, GS) ; Sydney Cord, Marrow Transplant Facility, Sydney Children's Hospital, High Street, Randwick NSW 2031, Australia (AD)

(Note : for Links provided by Atlas : click)


Other aliasIRF-1
LocusID (NCBI) 3659
Atlas_Id 40990
Location 5q31.1  [Link to chromosome band 5q31]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note Interferon regulatory factor 1 belongs to a family of transcription factors described for their role in regulating type I and type II interferons. Specifically, IRF1 has been identified as an activator of interferon alpha and beta transcription. Furthermore, it has been shown to play a role in the regulation of tumour suppression. IRF1 lies between interleukin (IL)-5 and CDC25C and is centromeric to IL-3 and GM-CSF. A number of mechanisms have been identified through which IRF1 is inactivated in various cancers. These, mechanisms include, deletion of the IRF1 region of chromosome 5q31; expression of IRF2; exon-skipping; binding of nucleophosmin; inactivation of tumour suppression by human papilloma viral oncogene, E7; and alternative splice variants lacking exons 7, 8, 9.


Description 7.72 kb with 10 exons and 9 introns.
Transcription 2.035kb mRNA. Coding sequence: CDS 198-1175.
IRF1 mRNA is expressed in low levels in a variety of tissues including, heart, lung, thymus, kidney and activated spleen.


Note IRF1 protein consists of 325 aa (36 kDa).
Description IRF1 protein has an half-life of approximately 30 min.
Localisation Nucleus
Function Transcriptional activator of type I interferons.


Note Deletion in 5q rearrangement of IRF1 are associated with preleukemic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). The most commonly reported cytogenetic abnormalities in leukaemia and preleukaemic myelodysplastic syndromes are found within 5q or loss of the entire choromosome 5. The most commonly deleted region was found to be 5q31. Willman et al. reported the tumour suppressor gene, IRF1 is situated within this 5q31 region . A common translocation found in AML is between chromosome 8q22 and chromosome 21q22. This translocation is found in approximately 40% of FAB-M2 AML and 8-20% of all AML.

Implicated in

Entity Acute Myeloid Leukaemia (AML)
Disease AML is an heterogenous disease representating clonal haematopoietic stem cell disorders. Initially classified under a French-American-British (FAB) co-operative group describing eight categories dependent on cell morphology on May-Grunwald-Giemsa (MGG) staining of peripheral blood and bone marrow smears. More recently, the World Health Organisation (WHO) proposed a new classification dependent on morphological, cytochemical, immunophenotypic, cytogenetic and molecular determinants that incorporates more recent developments in this disease and thereby reduce the limitations experienced under the FAB classification. Activation of the mutant N-ras gene in some myeloid cell lines induced growth suppression through IRF1.
Prognosis Prognosis is poor for most AML patients, depending on age and other unfavorable biological features.
Cytogenetics Translocations: t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(11;17)(q23;q21), or 11q23 rearrangements
Entity Preleukaemic Myelodysplastic Syndromes (MDS)
Note 30% of patients exhibit a deletion in chromosome 5q
Disease MDS is an heterogenous group of diseases representing clonal bone marrow disorders. They are characterised by cytopenias with ineffective haematopoisis often progressing despite bone marrow transplants and may result in acute myeloid leukaemia. Chromosomal abnormalities are commonly found in this disease.
Entity Breast Cancer
Disease The transcriptional regulation of human caspase-8 gene expression in the breast tumour cell line, MCF-7 was studied and found to be induced by IFN-gamma inducible transcription factor IRF1. Further studies have shown that IRF1 behaves as a tumour suppressor gene in breast cancer through caspase activation and induction of apoptosis. This suppression of apoptosis was observed independently of p53. Pizzoferrato et al., showed that ectopic expression of IRF1 using an adenovirus delivery system led to a decrease in survivin expression and an increase in cell death in breast cancer cell lines. This study also showed that p21 was up-regulated in IRF1-infected breast cancer cells independent of p53 modulation. Microarray analysis of clinically defined invasive breast carcinoma identified a negative correlation with IRF1 expression and tumour grade. High-grade breast carcinomas were found not to maintain IRF1 expression. IRF1 has also been shown to induce ligand-independent fas-associated death domain/caspase-8 mediated apoptosis in breast cancer cells.
Cytogenetics A single nucleotide polymorphism, A4396G in IRF1 was found to occur more frequently in breast cancer cell lines than in the general population. In addition, this polymorphism was more frequently expressed in the African American population than the European population.
Entity Cervical cancer
Note Alternative splicing of exons 7, 8 and 9 is implicated in cervical cancer.
Disease Lee et al., demonstrated that p27Kip1 inhibits hTERT mRNA expression and telomerase activity through post-transcriptional up-regulation by IFN-gamma/IRF-1 signalling.
Entity Gastric cancer
Note A point mutation in the second exon of the IRF1 gene with a methionine substituted with leucine at codon 8 was identified.
Disease Loss of heterozygosity at the IRF1 locus was found in 9 cases of histologically differentiated gastric adenocarcinomas. A mis-sense mutation in the residual allele was found in one case. This mutation in IRF1 was reported by Nozawa et al. to lead to reduced transcriptional activity but no change in its DNA-binding activity was observed. The loss of functional IRF1 is a key factor in development human gastric cancer.
Entity Oesophageal Cancer
Disease Oesophageal cancer is an aggressive tumour with two subtypes described, including: oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma. Following IFNgamma stimulation of three oesophageal cancer cell lines IRF1 was produced but did not lead to cell death. In contrast, adenoviral-IRF1 (Ad-IRF1) infection of these cell lines induced high IRF1 production resulting in apoptosis. Furthermore, a murine model of oesophageal cancer injected with Ad-IRF1 moderately inhibited tumour growth but did not induce tumour regression. Analysis of primary samples of oesophageal squamous cell carcinoma revealed decreased IRF1 expression and increased IRF2 expression compared to adjacent normal oesophageal tissue. In addition, overexpression of IRF1 inhibited tumorigenicity of ESCC cells when injected in vivo in nude mice.
Prognosis Ranked eighth most common malignancy and sixth most frequent cause of cancer worldwide.
Cytogenetics The most frequent occurance is loss of heterozygosity either single or multiple loci on chromosome 5q. The smallest deletion is found at 5q31.1 the same position for the IRF1 gene.
Entity Ovarian Cancer
Disease Interferon gamma has been shown to inhibit proliferation of a number of ovarian cancer cell lines in vitro. This growth inhibition and apoptotic effect in ovarian cancer cells was associated with a sustained increase in both IRF1 and p21. Kim et al., proposed a role for IRF1 in mediating IFNgamma-induced apoptosis through activation of caspase-1 gene expression in IFNgamma-sensitive ovarian cancer cells. IFNgamma was shown to induce IRF1 through the IFNgamma signalling pathway which in turn activated caspase-1. This was shown to lead to apoptosis of ovarian cancer cells, 2774 and PA-1, both sensitive to IFNgamma.
Prognosis Early stage diagnosis of epithelial ovarian cancer one can anticipate 90% survival. However, only 20-30% of patients with stage III epithelial ovarian carcinoma survive after 5 years.
Entity Melanoma
Disease Lowney et al., described evidence showing IRF1 protein expression correlated to morphologic characteristics associated with less advanced disease in human melanoma.
Entity Bladder Cancer
Disease Bladder cancer is ranked 9th in worldwide cancer incidence. A recent study determined that tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and downstream TRAIL-regulated apoptotic mechanisms are involved in IFNalpha-induced cell death in human bladder cancer cell line through a STAT1/IRF1-dependent pathway.


The A4396G polymorphism in interferon regulatory factor 1 is frequently expressed in breast cancer cell lines.
Bouker KB, Skaar TC, Harburger DS, Riggins RB, Fernandez DR, Zwart A, Clarke R
Cancer genetics and cytogenetics. 2007 ; 175 (1) : 61-64.
PMID 17498560
Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome.
Boultwood J, Fidler C, Lewis S, MacCarthy A, Sheridan H, Kelly S, Oscier D, Buckle VJ, Wainscoat JS
Blood. 1993 ; 82 (9) : 2611-2616.
PMID 8219215
Cytotoxic response of ovarian cancer cell lines to IFN-gamma is associated with sustained induction of IRF-1 and p21 mRNA.
Burke F, Smith PD, Crompton MR, Upton C, Balkwill FR
British journal of cancer. 1999 ; 80 (8) : 1236-1244.
PMID 10376977
Human interferon regulatory factor 1: intron-exon organization.
Cha Y, Sims SH, Romine MF, Kaufmann M, Deisseroth AB
DNA and cell biology. 1992 ; 11 (8) : 605-611.
PMID 1382447
The role of IRF1 and IRF2 transcription factors in leukaemogenesis.
Choo A, Palladinetti P, Passioura T, Shen S, Lock R, Symonds G, Dolnikov A
Current gene therapy. 2006 ; 6 (5) : 543-550.
PMID 17073600
Interferon regulatory factor 1 (IRF-1) and IRF-2 expression in breast cancer tissue microarrays.
Connett JM, Badri L, Giordano TJ, Connett WC, Doherty GM
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2005 ; 25 (10) : 587-594.
PMID 16241857
Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31).
Green WB, Slovak ML, Chen IM, Pallavicini M, Hecht JL, Willman CL
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 ; 13 (12) : 1960-1971.
PMID 10602416
Accelerated exon skipping of IRF-1 mRNA in human myelodysplasia/leukemia; a possible mechanism of tumor suppressor inactivation.
Harada H, Kondo T, Ogawa S, Tamura T, Kitagawa M, Tanaka N, Lamphier MS, Hirai H, Taniguchi T
Oncogene. 1994 ; 9 (11) : 3313-3320.
PMID 7936656
Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.
Harada H, Willison K, Sakakibara J, Miyamoto M, Fujita T, Taniguchi T
Cell. 1990 ; 63 (2) : 303-312.
PMID 2208287
Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in ovarian carcinoma cells.
Kim EJ, Lee JM, Namkoong SE, Um SJ, Park JS
Journal of cellular biochemistry. 2002 ; 85 (2) : 369-380.
PMID 11948692
Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity.
Kondo T, Minamino N, Nagamura-Inoue T, Matsumoto M, Taniguchi T, Tanaka N
Oncogene. 1997 ; 15 (11) : 1275-1281.
PMID 9315094
Alternative splicing variants of IRF-1 lacking exons 7, 8, and 9 in cervical cancer.
Lee EJ, Jo M, Park J, Zhang W, Lee JH
Biochemical and biophysical research communications. 2006 ; 347 (4) : 882-888.
PMID 16857162
IFN-gamma/IRF-1-induced p27kip1 down-regulates telomerase activity and human telomerase reverse transcriptase expression in human cervical cancer.
Lee SH, Kim JW, Oh SH, Kim YJ, Rho SB, Park K, Park KL, Lee JH
FEBS letters. 2005 ; 579 (5) : 1027-1033.
PMID 15710386
Interferon regulatory factor-1 and -2 expression in human melanoma specimens.
Lowney JK, Boucher LD, Swanson PE, Doherty GM
Annals of surgical oncology. 1999 ; 6 (6) : 604-608.
PMID 10493631
Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.
Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T
Cell. 1988 ; 54 (6) : 903-913.
PMID 3409321
Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients.
Navarro I, Ruiz MA, Cabello A, Collado R, Ferrer R, Hueso J, Martinez J, Miguel A, Orero MT, Pérez P, Nolasco A, Carbonell F
Leukemia research. 2006 ; 30 (8) : 971-977.
PMID 16423393
Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer.
Nozawa H, Oda E, Ueda S, Tamura G, Maesawa C, Muto T, Taniguchi T, Tanaka N
International journal of cancer. Journal international du cancer. 1998 ; 77 (4) : 522-527.
PMID 9679752
Common deleted region on the long arm of chromosome 5 in esophageal carcinoma.
Ogasawara S, Tamura G, Maesawa C, Suzuki Y, Ishida K, Satoh N, Uesugi N, Saito K, Satodate R
Gastroenterology. 1996 ; 110 (1) : 52-57.
PMID 8536888
Interferon-alpha induces TRAIL expression and cell death via an IRF-1-dependent mechanism in human bladder cancer cells.
Papageorgiou A, Dinney CP, McConkey DJ
Cancer biology & therapy. 2007 ; 6 (6) : 872-879.
PMID 17617740
A retroviral library genetic screen identifies IRF-2 as an inhibitor of N-ras-induced growth suppression in leukemic cells.
Passioura T, Shen S, Symonds G, Dolnikov A
Oncogene. 2005 ; 24 (49) : 7327-7336.
PMID 16007130
Distinct regions of frequent loss of heterozygosity of chromosome 5p and 5q in human esophageal cancer.
Peralta RC, Casson AG, Wang RN, Keshavjee S, Redston M, Bapat B
International journal of cancer. Journal international du cancer. 1998 ; 78 (5) : 600-605.
PMID 9808529
Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts.
Peterson LF, Boyapati A, Ahn EY, Biggs JR, Okumura AJ, Lo MC, Yan M, Zhang DE
Blood. 2007 ; 110 (3) : 799-805.
PMID 17412887
Ectopic expression of interferon regulatory factor-1 promotes human breast cancer cell death and results in reduced expression of survivin.
Pizzoferrato E, Liu Y, Gambotto A, Armstrong MJ, Stang MT, Gooding WE, Alber SM, Shand SH, Watkins SC, Storkus WJ, Yim JH
Cancer research. 2004 ; 64 (22) : 8381-8388.
PMID 15548708
Alterations in IRF1/IRF2 expression in acute myelogenous leukemia.
Preisler HD, Perambakam S, Li B, Hsu WT, Venugopal P, Creech S, Sivaraman S, Tanaka N
American journal of hematology. 2001 ; 68 (1) : 23-31.
PMID 11559933
The up-regulation of human caspase-8 by interferon-gamma in breast tumor cells requires the induction and action of the transcription factor interferon regulatory factor-1.
Ruiz-Ruiz C, Ruiz de Almodóvar C, Rodríguez A, Ortiz-Ferrón G, Redondo JM, López-Rivas A
The Journal of biological chemistry. 2004 ; 279 (19) : 19712-19720.
PMID 14993214
Recent advances in myelodysplastic syndromes.
Shadduck RK, Latsko JM, Rossetti JM, Haq B, Abdulhaq H
Experimental hematology. 2007 ; 35 (4 Suppl 1) : 137-143.
PMID 17379099
Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells.
Stang MT, Armstrong MJ, Watson GA, Sung KY, Liu Y, Ren B, Yim JH
Oncogene. 2007 ; 26 (44) : 6420-6430.
PMID 17452973
Acute myeloid leukemia.
Stone RM, O'Donnell MR, Sekeres MA
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program. 2004 : 98-117.
PMID 15561679
Involvement of IFN regulatory factor (IRF)-1 and IRF-2 in the formation and progression of human esophageal cancers.
Wang Y, Liu DP, Chen PP, Koeffler HP, Tong XJ, Xie D
Cancer research. 2007 ; 67 (6) : 2535-2543.
PMID 17363571
Ad-IRF-1 induces apoptosis in esophageal adenocarcinoma.
Watson GA, Queiroz de Oliveira PE, Stang MT, Armstrong MJ, Gooding WE, Kuan SF, Yim JH, Hughes SJ
Neoplasia (New York, N.Y.). 2006 ; 8 (1) : 31-37.
PMID 16533423
Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia.
Willman CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF
Science (New York, N.Y.). 1993 ; 259 (5097) : 968-971.
PMID 8438156


This paper should be referenced as such :
Palladinetti, P ; Symonds, G ; Dolnikov, A
IRF1 (interferon regulatory factor 1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):367-370.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)3659
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
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indexed on : Thu Oct 18 17:40:08 CEST 2018

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