Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene. [4] [5]
Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene. [4] [5]
Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially described as a transcription factor able to activate expression of the cytokine Interferon beta, [6] IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes. IRF-1 regulates expression of target genes by binding to an interferon stimulated response element (ISRE) in their promoters. The IRF-1 protein binds to the ISRE via an N-terminal helix-turn-helix DNA binding domain, [7] which is highly conserved among all IRF proteins.
Beyond its function as a transcription factor, IRF-1 has also been shown to trans-activate the tumour suppressor protein p53 through the recruitment of its co-factor p300. [8]
IRF-1 has been shown to play roles in the immune response, regulating apoptosis, DNA damage and tumor suppression. [9]
It has been shown that the extreme C-terminus of IRF-1 regulates its ability to activate transcription, nanobodies targeting this domain (MF1) are able to increase IRF-1 activity. [10]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Abnormal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Tail epidermis wholemount | Abnormal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Eye Histopathology | Normal |
| Citrobacter infection | Normal [11] |
| All tests and analysis from [12] [13] |
Model organisms have been used in the study of IRF1 function. A conditional knockout mouse line, called Irf1tm1a(EUCOMM)Wtsi [14] [15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. [16] [17] [18]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [12] [19] Twenty five tests were carried out and two phenotypes were reported. Homozygous mutant animals had abnormal peripheral blood lymphocytes, specifically decreased CD8-positive T cell and NK cell numbers and an increase in CD4-positive T cells. The mice also had an abnormal integument phenotype determined by a study of tail epidermis. [12]
IRF1 has been shown to interact with:
Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.
Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons. Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF-element (IRF-E) motifs, which is located upstream of the interferon genes. Some viruses have evolved defense mechanisms that regulate and interfere with IRF functions to escape the host immune system. For instance, the remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein. The Kaposi sarcoma herpesvirus, KSHV, is a cancer virus that encodes four different IRF-like genes; including vIRF1, which is a transforming oncoprotein that inhibits type 1 interferon activity. In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA methylation.
P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53.
Signal transducer and activator of transcription 1 (STAT1) is a transcription factor which in humans is encoded by the STAT1 gene. It is a member of the STAT protein family.
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.
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Interferon regulatory factor 2 is a protein that in humans is encoded by the IRF2 gene.
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.
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Interferon alpha-2 is a protein that in humans is encoded by the IFNA2 gene.
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Interferon regulatory factor 4 (IRF4) also known as MUM1 is a protein that in humans is encoded by the IRF4 gene,. IRF4 functions as a key regulatory transcription factor in the development of human immune cells. The expression of IRF4 is essential for the differentiation of T lymphocytes and B lymphocytes as well as certain myeloid cells. Dysregulation of the IRF4 gene can result in IRF4 functioning either as an oncogene or a tumor-suppressor, depending on the context of the modification.
Interferon regulatory factor 9 is a protein that in humans is encoded by the IRF9 gene, previously known as ISGF3G.
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene. The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.
Interferon regulatory factor 8 (IRF8) also known as interferon consensus sequence-binding protein (ICSBP), is a protein that in humans is encoded by the IRF8 gene. IRF8 is a transcription factor that plays critical roles in the regulation of lineage commitment and in myeloid cell maturation including the decision for a common myeloid progenitor (CMP) to differentiate into a monocyte precursor cell.
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Mitochondrial antiviral-signaling protein (MAVS) is a protein that is essential for antiviral innate immunity. MAVS is located in the outer membrane of the mitochondria, peroxisomes, and mitochondrial-associated endoplasmic reticulum membrane (MAM). Upon viral infection, a group of cytosolic proteins will detect the presence of the virus and bind to MAVS, thereby activating MAVS. The activation of MAVS leads the virally infected cell to secrete cytokines. This induces an immune response which kills the host's virally infected cells, resulting in clearance of the virus.
Zinc finger protein 143 is a protein that in humans is encoded by the ZNF143 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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