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RIPK1 In Cell Death Pathways
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK. RIPK1 is an enzyme that in humans is encoded by the ''RIPK1'' gene, which is located on chromosome 6. This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of 7 members, RIPK1 being the first member of the family. Structure RIPK1 protein is composed of 671 amino acids, and has a molecular weight of about 76 kDa. It contains a serine/threonine kinase domain (KD) in the 300 aa N-Terminus, a death domain (DD) in the 112 aa C-Terminus, and a central region between the KD and DD called intermediate domain (ID). *The kinase domain plays different roles in cell survival and is important in necroptosis induction. RIP interacts with TRAF2 vi ...
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Cell Death
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as diseases, localized injury, or the death of the organism of which the cells are part. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or injury. Programmed cell death Programmed cell death (PCD) is cell death mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits separate. PCD serves fundamental functions during both plant and metazoa (multic ...
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Optineurin
Optineurin is a protein that in humans is encoded by the ''OPTN'' gene. Function This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Model organisms Model organisms have been used in the study of OPTN function. A conditional knockout mouse line, called ''Optntm1a(EUCOMM)Wtsi'' was generated as part of ...
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Tumor Necrosis Factor Superfamily
The tumor necrosis factor (TNF) superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine. These proteins are expressed predominantly by immune cells and they regulate diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis. The superfamily contains 19 members that bind to 29 members of TNF receptor superfamily. An occurrence of orthologs in invertebrates hints at ancient origin of this superfamily in evolution. The PROSITE pattern of this superfamily is located in a beta sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydr ...
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Necroptosis
Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. The discovery of necroptosis showed that cells can execute necrosis in a programmed fashion and that apoptosis is not always the preferred form of cell death. Furthermore, the immunogenic nature of necroptosis favors its participation in certain circumstances, such as aiding in defence against pathogens by the immune system. Necroptosis is well defined as a viral defense mechanism, allowing the cell to undergo "cellular suicide" in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to being a response to disease, necroptosis has also been characterized as a component of inflammatory diseases such as Crohn's disease, pancreatitis, and myocardial infarction. ...
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RIPK1 In Cell Death Pathways
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK. RIPK1 is an enzyme that in humans is encoded by the ''RIPK1'' gene, which is located on chromosome 6. This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of 7 members, RIPK1 being the first member of the family. Structure RIPK1 protein is composed of 671 amino acids, and has a molecular weight of about 76 kDa. It contains a serine/threonine kinase domain (KD) in the 300 aa N-Terminus, a death domain (DD) in the 112 aa C-Terminus, and a central region between the KD and DD called intermediate domain (ID). *The kinase domain plays different roles in cell survival and is important in necroptosis induction. RIP interacts with TRAF2 vi ...
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Toll-like Receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles (because they are sensors of nucleic acids). TLRs received their name from their similarity to the protein coded by the toll gene. Function The ability of the immune s ...
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Mitogen-activated Protein
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. MAP kinases are found in eukaryotes only, but they are fairly diverse and encountered in all animals, fungi and plants, and even in an array of unicellular eukaryotes. MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). Discovery The first mitogen-activated protein kinase to be discovered was ERK1 (MAPK3) in mammals. Since ERK1 and its close relative ERK2 (MAPK1) are both involved in growth factor signaling, the family was t ...
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IκB Kinase
The IκB kinase (IkappaB kinase or IKK) is an enzyme complex that is involved in propagating the cellular response to inflammation. The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade. The IκBα (inhibitor of nuclear factor kappa B) protein inactivates the NF-κB transcription factor by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. Specifically, IKK phosphorylates the inhibitory IκBα protein. This phosphorylation results in the dissociation of IκBα from NF-κB. NF-κB, which is now free, migrates into the nucleus and activates the expression of at least 150 genes; some of which are anti-apoptotic. Catalyzed reaction In enzymology, an IκB kinase () is an enzyme that catalyzes the chemical reaction: :ATP + IκB protein \rightleftharpoons ADP + IκB phosphoprotein Thus, the two substrates of this enzyme are ATP and IκB protein, whereas its tw ...
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IKBKG
NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the ''IKBKG'' gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28. Multiple transcript variants encoding different isoforms have been found for this gene. Function NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Clinical significance Mutations in the IKBKG gene results in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. Incontinentia Pigmenti (IP) is an X-linked dominant disease caused by a mutation in the IKBKG gene. Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis, a lack ...
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RIPK1 In Cell Survival
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK. RIPK1 is an enzyme that in humans is encoded by the ''RIPK1'' gene, which is located on chromosome 6. This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of 7 members, RIPK1 being the first member of the family. Structure RIPK1 protein is composed of 671 amino acids, and has a molecular weight of about 76 kDa. It contains a serine/threonine kinase domain (KD) in the 300 aa N-Terminus, a death domain (DD) in the 112 aa C-Terminus, and a central region between the KD and DD called intermediate domain (ID). *The kinase domain plays different roles in cell survival and is important in necroptosis induction. RIP interacts with TRAF ...
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C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Chemistry Each amino acid has a carboxyl group and an amine group. Amino acids link to one another to form a chain by a dehydration reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an unbound amine group, the N-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus. Function C-terminal retention signals While the N-terminus of a protein often con ...
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Caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions. The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues. Caspases have other identified roles in programmed ...
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