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Interferon Regulatory Factor
Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression). 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. Role in IFN Signaling IRFs primarily regulate type I IFNs in the host ...
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Transcription (genetics)
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA ( Human genome#Coding vs. noncoding DNA), while at least 80% of mammalian genomic DNA can be actively transcribed (in one or more types of cells), with the majority of this 80% considered to be ncRNA. Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription proceeds in the following general steps: # RNA polymerase, together with one or more general transcription factors, binds to promoter DNA ...
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IRF1
Interferon regulatory factor 1 is a protein that in humans is encoded by the ''IRF1'' gene. Function 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, 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, 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. IRF-1 has been shown to play roles in the immune response, regulating apoptosis, DNA damage and tumo ...
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Myeloid Tissue
Myeloid tissue, in the bone marrow sense of the word '' myeloid'' ('' myelo-'' + ''-oid''), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (''myelo-'' + '' -genous'') is any tissue of, or arising from, bone marrow; in these senses the terms are usually used synonymously, as for example with chronic myeloid/myelogenous leukemia. In hematopoiesis, myeloid or myelogenous cells are blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets (the common myeloid progenitor, that is, CMP or CFU-GEMM), or in a narrower sense also often used, specifically from the lineage of the myeloblast (the myelocytes, monocytes, and their daughter types). Thus, although all blood cells, even lymphocytes, are normally born in the bone marrow in adults, myeloid cells in the narrowest sense of the term can be distinguished from lymphoid cells, that is, lymphocytes, which come from common lymphoid pr ...
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Dendritic Cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the ''dendrites'' that give the cell its name (δένδρον or déndron being Greek for 'tree'). While similar in appearance, these are structures ...
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IRF8
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. Function Interferon Consensus Sequence-binding protein (ICSBP) is a transcription factor of the interferon regulatory factor ( IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-α and IFN-β. IRF family proteins also control expression of IFN-α and IFN-β-regulated genes that are induced by viral infection. ...
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Innate Immune System
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms (see Beyond vertebrates).. The major functions of the innate immune system are to: * recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines * activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells * identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells * activate the adaptive immune system through antigen presentation * act as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical measures such a ...
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Repressor
In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes into messenger RNA. An RNA-binding repressor binds to the mRNA and prevents translation of the mRNA into protein. This blocking or reducing of expression is called repression. Function If an inducer, a molecule that initiates the gene expression, is present, then it can interact with the repressor protein and detach it from the operator. RNA polymerase then can transcribe the message (expressing the gene). A co-repressor is a molecule that can bind to the repressor and make it bind to the operator tightly, which decreases transcription. A repressor that binds with a co-repressor is termed an ''aporepressor'' or ''inactive repressor''. One type of aporepressor is the trp repressor, a ...
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IRF4
Interferon regulatory factor 4 (IRF4) also known as ''MUM1'' is a protein that in humans is encoded by the ''IRF4'' gene, located at 6p25-p23. IRF4 functions as a key regulatory transcription factor in the development of human immune cells.Nam S, Lim J-S (2016). "Essential role of interferon regulatory factor 4 (IRF4) in immune cell development." ''Arch. Pharm. Res''. 39: 1548–1555doi:10.1007/s12272-016-0854-1Shaffer AL, Tolga Emre NC, Romesser PB, Staudt LM (2009). "IRF4: Immunity. Malignancy! Therapy?" ''Clinical Cancer Research''. 15 (9): 2954-2961doi:10.1158/1078-0432.CCR-08-1845/ref> The expression of IRF4 is essential for the differentiation of T lymphocytes and B lymphocytes as well as certain myeloid cells. The ''MUM1'' symbol is polysemous; although it is an older synonym for ''IRF4'' (HGNC:6119), it is also the current HGNC official symbol for melanoma associated antigen (mutated) 1 (HGNC:29641; located at 19p13.3). Dysregulation of the ''IRF4'' gene can result in ''IRF ...
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IRF2
Interferon regulatory factor 2 is a protein that in humans is encoded by the ''IRF2'' gene. Function IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. See also *IRF1 *Interferon regulatory factors Interactions IRF2 has been shown to interact with BRD7, EP300 and PCAF P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53. Structure Several domains of PCAF can act independently or in unison to enable its funct .... References Further reading * * * * * * * * * * * * * * * * * External links * * Transcription factors ...
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Inflammatory Cytokine
An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include interleukin-1 (IL-1), IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ), and granulocyte-macrophage colony stimulating factor (GM-CSF) and play an important role in mediating the innate immune response. Inflammatory cytokines are predominantly produced by and involved in the upregulation of inflammatory reactions. Excessive chronic production of inflammatory cytokines contribute to inflammatory diseases, that have been linked to different diseases, such as atherosclerosis and cancer. Dysregulation has also been linked to depression and other neurological diseases. A balance between proinflammatory and anti-inflammatory cytokines is necessary to maintain health. Aging and exercise also play a role ...
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IRF5
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. Function IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative splice variants encoding different isoforms exist. The regulatory and repression regions of the IRF family are mainly located in the C-terminal of the IRF. A 2020 study showed that an adaptor protein named TASL play an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif, drawing a similar analo ...
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TANK-binding Kinase 1
TBK1 (TANK-binding kinase 1) is an enzyme with kinase activity. Specifically, it is a serine / threonine protein kinase. It is encoded by the TBK1 gene in humans. This kinase is mainly known for its role in innate immunity antiviral response. However, TBK1 also regulates cell proliferation, apoptosis, autophagy, and anti-tumor immunity. Insufficient regulation of TBK1 activity leads to autoimmune, neurodegenerative diseases or tumorigenesis. Structure and regulation of activity TBK1 is a non-canonical IKK kinase that phosphorylates the nuclear factor kB (NFkB). It shares sequence homology with canonical IKK. The N-terminus of the protein contains the kinase domain (region 9-309) and the ubiquitin-like domain (region 310-385). The C-terminus is formed by two coiled-coil structures (region 407-713) that provide a surface for homodimerization. The autophosphorylation of serine 172, which requires homodimerization and ubiquitinylation of lysines 30 and 401, is necessary for kinase ...
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