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RIPK1
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, necroptosis, and PANoptosis 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PANoptosis
PANoptosis is a prominent innate immune, inflammatory, and lytic cell death pathway initiated by innate immune sensors and driven by caspases and receptor-interacting protein kinases (RIPKs) through multiprotein PANoptosome complexes. The assembly of the PANoptosome cell death complex occurs in response to germline-encoded pattern-recognition receptors (PRRs) sensing pathogens, including bacterial, viral, and fungal infections, as well as pathogen-associated molecular patterns, damage-associated molecular patterns, and cytokines that are released during infections, inflammatory conditions, and cancer. Several PANoptosome complexes, such as the ZBP1-, AIM2-, RIPK1-, NLRP3 and NLRC5- and NLRP12-PANoptosomes, have been characterized so far. Emerging genetic, molecular, and biochemical studies have identified extensive crosstalk among the molecular components across various cell death pathways in response to a variety of pathogens and innate immune triggers. Historically, inflamm ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RIPK3
Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that is encoded by the ''RIPK3'' gene in humans. The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. It contains a C-terminal domain unique from other RIP family members. The encoded protein is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce necroptosis by interaction with RIPK1 and MLKL in a protein complex termed the necrosome. Interactions between RIPK1 and RIPK3 also form a necrosome, which triggers apoptosis. Interactions RIPK3 has been shown to interact with RIPK1 to form an amyloid spine The RIP Homotypic Interaction Motifs (RHIM) of RIPK3 allows it to form a necrosome with RIPK1. This interaction makes heterotypic β sheets, which bind ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FADD
FAS-associated death domain protein, also called MORT1, is encoded by the ''FADD'' gene on the 11q13.3 region of chromosome 11 in humans. FADD is an Signal transducing adaptor protein, adaptor protein that bridges members of the Tumor necrosis factor receptor, tumor necrosis factor receptor superfamily, such as the FasR, Fas-receptor, to caspase 8, procaspases 8 and caspase 10, 10 to form the death-inducing signaling complex (DISC) during apoptosis. As well as its most well known role in apoptosis, FADD has also been seen to play a role in other processes including proliferation, cell cycle regulation and development. Structure FADD is a 23 kDa protein, made up of 208 amino acids. It contains two main domains: a C terminal death domain (DD) and an N terminal death effector domain (DED). Each domain, although sharing very little sequence similarity, are structurally similar to one another, with each consisting of 6 α helices. The DD of FADD binds to receptors such as the Fas r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TRADD
Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the ''TRADD'' gene. TRADD is an adaptor protein. Function The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/ TNFR1 and mediates programmed cell death signaling and NF-κB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/ FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway. Interactions TRADD has been shown to interact with: * FADD, * Keratin 18 * RIPK1, * STAT1, * TNFRSF1A, * TNFRSF25, and * TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 protein, single-spanning receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from Microorganism, 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. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in Intracellular receptor, intracellular Vesicle (biology and chemistry), vesicles (because they are sensors of nucleic acids). TLRs received their name ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ZBP1
Z-DNA-binding protein 1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, is a protein that in humans is encoded by the ''ZBP1'' gene. ZBP1 is also an abbreviation for chicken or rat β-actin zipcode-binding protein 1, a homolog of the human insulin-like growth factor 2 mRNA-binding protein 1 ( IMP-1) and murine CRD-BP, the proteins involved in mRNA transport ( RNA-binding proteins, RBPs). History ZBP1 was first identified as an interferon-inducible Z-NA binding protein, but its specific functions remained unclear for many years. It was initially thought to be a cytosolic DNA sensor. However, the generation of ''Zbp1''-deficient mice revealed that these mice responded normally to DNA and DNA virus infections, producing normal levels of interferon. Further insights came with the discovery of ZBP1's receptor-interacting protein homotypic interaction motif (RHIM) domains, which mediate interactions with other proteins. Experiments showed that ZBP ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 (cellular), 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. The term "cell necrobiology" has been used to describe the life processes associated with morphological, biochemical, and molecular changes which predispose, precede, and accompany cell death, as well as the consequences and tissue response to cell death. The word is derived from the Greek language, Greek νεκρό meaning "death", βìο meaning "life", and logos, λόγος meaning "the study of". The term was initially coined to bro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Caspase 8
Caspase-8 is a caspase protein, encoded by the ''CASP8'' gene. It most likely acts upon caspase-3. ''CASP8'' orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present in birds. Function The ''CASP8'' gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TNFR1
Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα). Function The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate the transcription factor NF-κB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor. Clinical significance Germline mutations of the extracellular domains of this receptor were found to be associated with the human genetic disorder called tumor necrosis factor associated periodic syndrom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the Inhibitor of apoptosis, IAP family members BIRC2, cIAP1 and BIRC3, cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
