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Type III Interferon
The type III interferon group is a group of anti-viral cytokines, that consists of four IFN-λ (lambda) molecules called IFN-λ1, IFN-λ2, IFN-λ3 (also known as IL29, IL28A and IL28B respectively), and IFN-λ4. They were discovered in 2003. Their function is similar to that of type I interferons, but is less intense and serves mostly as a first-line defense against viruses in the epithelium. Genomic location Genes encoding this group of interferons are all located on the long arm of chromosome 19 in human, specifically in region between 19q13.12 and 19q13.13. IFNL1 gene, encoding IL-29, is located downstream of IFNL2, encoding IL-28A. IFNL3, encoding IL28B, is located downstream of IFNL4. In mice, the genes encoding for type III interferons are located on chromosome 7 and the family consist only of IFN-λ2 and IFN-λ3. Structure Interferons All interferon groups belong to class II cytokine family which have a conserved structure that comprises six α-helices. The prote ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interferon
Interferons (IFNs, ) 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. IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. However, virus-encoded genetic elements have the ability to antagonize the IFN response contributing to viral pathogenesis and viral diseases. IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages, and they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
JAK-STAT Signaling Pathway
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors (which bind the chemical signals). Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system. Structure of JAKs and STATs ''Main articles: JAKs and STATs'' There are four JAK proteins: JAK1, JAK2, JAK3 and TYK2. JAKs contains a FERM domain (approximately 400 residues), an SH2-related domain (approximately 100 residues), a kinase domain (approximately 250 residues) and a pseudokinase doma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Reovirus
''Reoviridae'' is a family of double-stranded RNA viruses. Member viruses have a wide host range, including vertebrates, invertebrates, plants, protists and fungi. They lack lipid envelopes and package their segmented genome within multi-layered capsids. Lack of a lipid envelope has allowed three-dimensional structures of these large complex viruses (diameter ∼60–100 nm) to be obtained, revealing a structural and likely evolutionary relationship to the cystovirus family of bacteriophage. There are currently 97 species in this family, divided among 15 genera in two subfamilies. Reoviruses can affect the gastrointestinal system (such as rotaviruses) and respiratory tract. The name "reo-" is an acronym for "''r''espiratory ''e''nteric ''o''rphan" viruses''.'' The term " orphan virus" refers to the fact that some of these viruses have been observed not associated with any known disease. Even though viruses in the family ''Reoviridae'' have more recently been identified with var ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interferon Type I
The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cytoband over approximately 400 kb including coding genes for IFNα (''IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17'' and ''IFNA21''), IFNω (''IFNW1''), IFNɛ (''IFNE''), IFNк (''IFNK'') and IFNβ (''IFNB1''), plus 11 IFN pseudogenes. Interferons bind to interferon receptors. All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains. Type I IFNs are found in all mammals, and homologous (similar) molecules have been found in birds, reptiles, amphibians and fish species. Sources and functions IFN-α and IFN-β are secreted by many cell types including lymphocytes ( NK cells, B-cells and T-cells), macrophages, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Suppressor Of Cytokine Signalling
SOCS (suppressor of cytokine signaling proteins) refers to a family of genes involved in inhibiting the JAK-STAT signaling pathway. Genes * CISH * SOCS1 * SOCS2 * SOCS3 Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the ''SOCS3'' gene. This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. ... * SOCS4 * SOCS5 * SOCS6 * SOCS7 Structure All SOCS have certain structures in common. This includes a varying N-terminal domain involved in protein-protein interactions, a central SH2 domain, which can bind to molecules that have been phosphorylated by tyrosine kinases, and a SOCS box located at the C-terminal that enables recruitment of E3 ligases and ubiquitin signaling molecules. Discovery The first protein to be classified as a suppressor of cytokine signaling, CIS (cytokine-inducible SH2), was discovered in 1995, when it was found to have a unique abil ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
OAS1
2'-5'-oligoadenylate synthetase 1 is an enzyme that in humans is encoded by the ''OAS1'' gene. This gene encodes a member of the 2-5A synthetase family, which include essential proteins involved in the innate immune response to viral infection. The encoded protein is induced by interferons and uses adenosine triphosphate in 2'-specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates (2-5As). These molecules activate latent RNase L, which results in both viral and endogenous RNA degradation and the inhibition of viral replication. The three known members of this gene family are located in a cluster on chromosome 12. Hypomorphic mutations in this gene have been associated with host susceptibility to viral infection, while gain-of-function variants can cause autoinflammatory Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythema ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interferon Regulatory Factors
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory. Discovery NF-κB was discovered by Ranjan Sen in the lab of Nobel laureate David Baltimore via its interaction with an 11-base pair sequence in the immunoglobulin light-chain enhancer in B cells. Later work by Alexander Poltorak and Bruno Lemaitre in mice and ''Drosophila'' fr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interferon-stimulated Gene
An interferon-stimulated gene (ISG) is a gene that can be expressed in response to stimulation by interferon. Interferons bind to receptors on the surface of a cell, initiating protein signaling pathways within the cell. This interaction leads to the expression of a subset of genes involved in the innate immune system response. ISGs are commonly expressed in response to viral infection, but also during bacterial infection and in the presence of parasites. Expression ISGs are genes whose expression can be stimulated by interferon, but may also be stimulated by other pathways. Interferons are a type of protein called a cytokine, which is produced in response to infection. When released, they signal to infected cells and other nearby cells that a pathogen is present. This signal is passed from one cell to another by binding of the interferon to a cell surface receptor on a naïve cell. The receptor and interferon are taken inside the cell while bound to initiate expression of ISG ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
STAT2
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the ''STAT2'' gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). STAT2 sequence identity between mouse and human is only 68%. Function The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to IFN, this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (IRF9) and form ISGF-3 (IFN-stimulated gene factor-3), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. ISGF-3 proceeds the activation of genes via the IFN-stimulated response element (ISRE). ISRE-driven genes include Ly-6 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
STAT1
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. Function All STAT molecules are phosphorylated by receptor associated kinases, that causes activation, dimerization by forming homo- or heterodimers and finally translocate to nucleus to work as transcription factors. Specifically STAT1 can be activated by several ligands such as Interferon alpha (IFNα), Interferon gamma (IFNγ), Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), Interleukin 6 (IL-6), or IL-27. Type I interferons (IFN-α, IFN-ß) bind to receptors, cause signaling via kinases, phosphorylate and activate the Jak kinases TYK2 and JAK1 and also STAT1 and STAT2. STAT molecules form dimers and bind to ISGF3G/IRF-9, which is Interferon stimulated gene factor 3 complex with Interferon regulatory Factor 9. This allows STAT1 to enter the nucleus. STAT1 has a key role in many ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Kinase 2
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the ''TYK2'' gene. Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3). It has been implicated in IFN-α, IL-6, IL-10 and IL-12 signaling. Function This gene encodes a member of the tyrosine kinase and, to be more specific, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. Cytokines play pivotal roles in immunity and inflammation by regulating the survival, proliferation, differentiation, and function of immune cells, as well as cells from other organ systems. Hence, targeting cytokines and their receptors is an effective means of treating such di ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
