IRF1
a transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation 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. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58, TRAIL, OAS1/2, PIAS1, PKR and RSAD2; antibacterial response, such as iNOS; anti- proliferative response, such as p53, LOX and CDKN1A; apoptosis, such as PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, COX-2 and CYBB; DNA damage responses and DNA repair, such as POLQ; MHC class I expression, such as TAP1, PSMB9, PSME1, PSME2 and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53. 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. Defects in IRF1 are a cause of gastric adenocarcinoma (GASC), accounting for most of all gastric malignant tumors. Deletions or rearrangements of IRF1 can occur in preleukemic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Note: This description may include information from UniProtKB.
Molecular Function: protein binding; DNA binding; sequence-specific DNA binding; transcription factor activity
Biological Process: transcription from RNA polymerase II promoter; negative regulation of tyrosine phosphorylation of Stat1 protein; I-kappaB kinase/NF-kappaB cascade; regulation of cell cycle; positive regulation of transcription, DNA-dependent; female pregnancy; protein amino acid phosphorylation; negative regulation of cell proliferation; regulation of adaptive immune response; negative regulation of regulatory T cell differentiation; positive regulation of interferon-beta production; positive regulation of interferon type I production; cell cycle arrest; defense response to virus; CD8-positive, alpha-beta T cell differentiation; cytokine and chemokine mediated signaling pathway; regulation of MyD88-dependent toll-like receptor signaling pathway; regulation of innate immune response; protein amino acid acetylation; positive regulation of interleukin-12 biosynthetic process; response to heat; induction of apoptosis; positive regulation of transcription from RNA polymerase II promoter; blood coagulation; negative regulation of transcription, DNA-dependent
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.
