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Interferon-Regulatory Factor Transcription Factors Proteins

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Interferon-Regulatory Factor Transcription Factors Proteins

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Interferon-Regulatory Factor Transcription Factors Proteins Background

Interferon regulatory factor (IRF) is a protein that regulates interferon transcription. They are used in the JAK-STAT signaling pathway. The interferon regulatory factor contains a conserved N-terminal region of approximately 120 amino acids that folds into a structure that specifically binds to the interferon consensus sequence (ICS), which is located upstream of the interferon gene. The remainder of the interferon regulatory factor sequence varies depending on the precise function of the protein. Kaposi sarcoma herpesvirus KSHV is a cancer virus that encodes four different IRF-like genes; including vIRF1, a transforming oncoprotein that inhibits type 1 interferon activity. Furthermore, expression of the IRF gene is epigenetically regulated by promoter methylation.

Interferon regulatory factor transcription factor. Figure 1. Interferon regulatory factor transcription factor.

Genes

IRF1

Interferon regulatory factor 1 is a protein encoded by the IRF1 gene in humans. IRF1 is the first member of the identified interferon-regulated transcription factor (IRF) family. Originally described as a transcription factor capable of activating cytokine interferon beta expression, it was subsequently shown that IRF-1 acts as a transcriptional activator or repressor of multiple target genes.

Structure of the IRF1 protein. Figure 2. Structure of the IRF1 protein.

IRF2 encodes an interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits IRF1-mediated transcriptional activation of interferon alpha and beta, and may be other genes that use IRF1 for transcriptional activation.

 Structure of the IRF2 proteinFigure 3. Structure of the IRF2 protein

IRF3 is a member of the interferon regulated transcription factor (IRF) family. IRF3 was originally discovered as a homologue of IRF1 and IRF2. IRF3 has been further characterized and shown to contain several functional domains, including nuclear export signals, DNA binding domains, C-terminal IRF association domains and several regulatory phosphorylation sites.

 Structure of the IRF3 proteinFigure 4. Structure of the IRF3 protein

Interferon regulatory factor 4 also known as MUM1 is a protein that in humans is encoded by the IRF4 gene, located at 6p25-p23.

 Structure of the IRF4 proteinFigure 5. Structure of the IRF4 protein

IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including viral-mediated interferon activation, as well as regulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA binding domain comprising a tryptophan (W) repeat.

This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly conserved N-terminal helix-turn-helix DNA binding domain and a less conserved C-terminal protein binding domain. The function of IRF6 is related to the formation of connective tissue, such as the connective tissue of sputum. This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Furthermore, it has been observed that the IRF6 gene undergoes epigenetic regulation by promoter methylation.

IRF7 encodes an interferon regulatory factor 7, and interferon regulatory factor 7 is a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of viral-induced cellular genes, including type I interferon genes. In particular, IRF7 regulates many interferon-alpha genes.

IRF8, also known as interferon consensus sequence binding protein (ICSBP), is a protein encoded by the IRF8 gene in humans. IRF8 is a transcription factor that plays a key role in lineage typing and regulation of myeloid cell maturation, including the determination of common myeloid progenitor cells (CMP) to differentiate into monocyte precursor cells.

Interferon regulatory factor 9 is a protein encoded by the IRF9 gene in humans, formerly known as ISGF3G. IRF9 has been shown to interact with STAT2 and STAT1 (Figure 6). IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I interferon genes. In particular, IRF7 regulates many interferon-alpha genes.

 Structure of STAT1.Figure 6. Structure of STAT1.

Interferon

Interferon (IFN) is a group of signaling proteins that are produced and released by host cells in response to the presence of several viruses. In a typical situation, virus-infected cells release interferon, causing nearby cells to strengthen their antiviral defenses. IFN belongs to a large class of proteins called cytokines, and molecules used for intercellular communication trigger protective defenses of the immune system and help eradicate pathogens. Interferon is named for its ability to "interfere" with viral replication by protecting cells from viral infection. IFNs also have a variety of other functions: they activate immune cells, such as natural killer cells and macrophages; they increase host defense by upregulating antigen presentation by increasing the expression of major histocompatibility complex (MHC) antigens. Certain symptoms of infection, such as fever, muscle aches and "flu-like symptoms," are also caused by the production of IFN and other cytokines. More than 20 different IFN genes and proteins have been identified in animals including humans. They are usually divided into three categories: type I IFN, type II IFN and type III IFN. IFNs belonging to all three classes are important for the regulation of viral infections and the immune system.

References:

1. Espinosa V.; et al. Type III interferon is a critical regulator of innate antifungal immunity. Science Immunology. 2017,2 (16): eaan5357.

2. Sharieff KA.; et al. Advances in treatment of chronic hepatitis C: 'pegylated' interferons. Cleveland Clinic Journal of Medicine. 2002,69 (2): 155–9.

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