IRF1

The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]

Interferon Regulatory Factor 1

Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195, PubMed:32385160).
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 (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195).
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 (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:21389130, PubMed:22367195).
Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters (PubMed:32385160).
Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, 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 (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195).
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 (PubMed:18641303, PubMed:22200613).
Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53 (PubMed:15509808, PubMed:18084608).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750).
Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750).
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 (PubMed:20049431).

Apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
CD8-positive, alpha-beta T cell differentiationIEA:Ensembl
Cellular response to interferon-betaManual Assertion Based On ExperimentIDA:BHF-UCL
Cellular response to mechanical stimulusManual Assertion Based On ExperimentIEP:UniProtKB
Defense response to virusManual Assertion Based On ExperimentIDA:UniProtKB
Immune system processManual Assertion Based On ExperimentIBA:GO_Central
Interferon-gamma-mediated signaling pathwayISS:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of regulatory T cell differentiationISS:UniProtKB
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of interferon-beta productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of interleukin-12 productionIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of type I interferon productionISS:UniProtKB
Regulation of adaptive immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of CD8-positive, alpha-beta T cell proliferationISS:UniProtKB
Regulation of cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of innate immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of MyD88-dependent toll-like receptor signaling pathwayISS:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central

Cytoplasm; Nucleus. MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1.

Gastric cancer (GASC):
A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.

Phosphorylated by CK2 and this positively regulates its activity.
Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation (PubMed:17942705).
Sumolyated by UBE2I/UBC9 and SUMO1 (By similarity).
Inactivates the tumor suppressor activity (PubMed:17942705).
Elevated levels in tumor cells (PubMed:17942705).
Major site is Lys-275 (PubMed:17942705).
Sumoylation is enhanced by PIAS3 (By similarity).
Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (PubMed:17942705).
Ubiquitinated. Appears to compete with sumoylation on C-terminal sites.