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Interferon regulatory factor 1

Definition:

Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, RIGI, TNFSF10/TRAIL, ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1/IRG1. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.

References:

[1]. Andrea Kröger, et al. Activities of IRF-1. J Interferon Cytokine Res. 2002 Jan;22(1):5-14. [Content Brief]

[2]. T Taniguchi, et al. IRF family of transcription factors as regulators of host defense. Annu Rev Immunol. 2001;19:623-55. [Content Brief]

[3]. Giovanna Romeo, et al. IRF-1 as a negative regulator of cell proliferation. J Interferon Cytokine Res. 2002 Jan;22(1):39-47. [Content Brief]

[4]. David Savitsky, et al. Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother. 2010 Apr;59(4):489-510. [Content Brief]

[5]. David Dornan, et al. Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53. Mol Cell Biol. 2004 Nov;24(22):10083-98. [Content Brief]

[6]. Kenya Honda, et al. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006 Sep;6(9):644-58. [Content Brief]

[7]. Junsoo Park, et al. Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17028-33. [Content Brief]

[8]. Zao-Zhong Su, et al. Central role of interferon regulatory factor-1 (IRF-1) in controlling retinoic acid inducible gene-I (RIG-I) expression. J Cell Physiol. 2007 Nov;213(2):502-10. [Content Brief]

[9]. Alessandra Fragale, et al. IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression. J Immunol. 2008 Aug 1;181(3):1673-82. [Content Brief]

[10]. Yunlong Huang, et al. Type I interferons and interferon regulatory factors regulate TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages. PLoS One. 2009;4(4):e5397. [Content Brief]

[11]. Tim D D Somerville, et al. ZBED2 is an antagonist of interferon regulatory factor 1 and modifies cell identity in pancreatic cancer. Proc Natl Acad Sci U S A. 2020 May 26;117(21):11471-11482. [Content Brief]

[12]. J Gao, et al. IRF-1 transcriptionally upregulates PUMA, which mediates the mitochondrial apoptotic pathway in IRF-1-induced apoptosis in cancer cells. Cell Death Differ. 2010 Apr;17(4):699-709. [Content Brief]

[13]. Michelle L Bowie, et al. IRF-1 promotes apoptosis in p53-damaged basal-type human mammary epithelial cells: a model for early basal-type mammary carcinogenesis. Adv Exp Med Biol. 2008;617:367-74. [Content Brief]

[14]. Valentina Muto, et al. Human papillomavirus type 16 E5 protein induces expression of beta interferon through interferon regulatory factor 1 in human keratinocytes. J Virol. 2011 May;85(10):5070-80. [Content Brief]

[15]. Hongyan Qi, et al. Interferon regulatory factor 1 transactivates expression of human DNA polymerase η in response to carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. J Biol Chem. 2012 Apr 13;287(16):12622-33. [Content Brief]

[16]. Shigeru Oshima, et al. Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. Mol Cell Biol. 2004 Jul;24(14):6298-310. [Content Brief]

[17]. Michaele J Armstrong, et al. Interferon Regulatory Factor 1 (IRF-1) induces p21(WAF1/CIP1) dependent cell cycle arrest and p21(WAF1/CIP1) independent modulation of survivin in cancer cells. Cancer Lett. 2012 Jun 1;319(1):56-65. [Content Brief]

[18]. Christos I Maratheftis, et al. RNA interference of interferon regulatory factor-1 gene expression in THP-1 cell line leads to Toll-like receptor-4 overexpression/activation as well as up-modulation of annexin-II. Neoplasia. 2007 Dec;9(12):1012-20. [Content Brief]

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