AICD (activation-induced cell death) is programmed cell death caused by the interaction of Fas receptors (Fas, CD95) and Fas ligands (FasL, CD95 ligand). AICD is a negative regulator of activated T lymphocytes that results from repeated stimulation of their T-cell receptors (TCR) and helps to maintain peripheral immune tolerance. Alteration of the process may lead to autoimmune diseases.
The AICD effector cell is one that expresses FasL, and apoptosis is induced in the cell expressing the Fas receptor. Both activated T cells and B cells express Fas and undergo clonal deletion by the AICD mechanism. Activated T cells that express both Fas and FasL may be killed by themselves or by each other.
The binding of Fas ligand to Fas receptor triggers trimerization of Fas, whose cytoplasmic domain is then able to bind the death domain of the adaptor protein FADD (Fas-associated protein with death domain). Procaspase 8 binds to FADD's death effector domain (DED) and proteolytically self-activates as caspase 8. Fas, FADD, and procaspase 8 together form a death-inducing signaling complex (DISC). Activated caspase 8 is released into the cytosol, where it activates the caspase cascade that initiates apoptosis.
FasL is primarily regulated at the transcriptional level. (The other option is regulation of the signal emanating from the death receptor itself, controlling sensitivity to the induction of apoptosis.) NFAT activated by TCR stimulation activates FasL transcription, possibly indirectly by upregulating early growth response proteins. T cell activation-induced transcription of FasL is further regulated by c-Myc–MAX heterodimers, and can be blocked by c-Myc downregulation. Interferon regulatory factors IRF1 and IRF2 also upregulate FasL transcription by directly binding to the FasL promoter.
The acronym AICD may refer to:
Automated Implantable Cardioverter-Defibrillator
Amyloid precursor protein Intracellular Cytoplasmic/C-terminal Domain, the smaller cleavage product of APP by gamma-secretase
Australian Institute of Company Directors, an organisation supporting company directors in Australia
Activation-induced cell death (AICD), important for maintaining T cell homeostasis of the immune system. Autoreactive T cells undergo apoptosis through AICD both from the thymus and peripheryActivated PI3K delta syndrome
Activated PI3K delta syndrome is a primary immunodeficiency disease caused by activating gain of function mutations in the PIK3CD gene. Which encodes the p110δ catalytic subunit of PI3Kδ, APDS-2 (PASLI-R1) is caused by exon-skipping mutations in PIK3R1 which encodes for the regulatory subunit p85α. APDS and APDS-2 affected individuals present with similar symptoms, which include increased susceptibility to airway infections, bronchiectasis and lymphoproliferation.CD134
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels.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, or may result from such factors as disease, 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.DGKA
Diacylglycerol kinase alpha is an enzyme that in humans is encoded by the DGKA gene.The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified.DNAJA3
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.Douglas R. Green
Douglas Green (born 1955), is an American biologist. He holds the Peter C. Doherty Endowed Chair of Immunology in St. Jude Children's Research Hospital. Green received his PhD from Yale.
His research has focused on the process of active cell death and cell survival, extending from the role of cell death in cancer regulation and immune responses in the whole organism to the fundamental molecular events directing the death of the cell. Green is editor in chief of the Nature Publishing Group journal Oncogene (journal). He is the author of the book Cell Death, Means To An End.Extracellular signal-regulated kinases
In molecular biology, extracellular signal–regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.The term, "extracellular signal–regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase (MAPK), but has more recently been adopted for a specific subset of the mammalian MAPK family.In the MAPK/ERK pathway, Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1, and some downstream protein kinases.
Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.Fas ligand
Fas ligand (FasL or CD95L) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.Flavagline
Flavaglines are a family of natural products that are found in plants of the genus Aglaia (Meliaceae). These compounds are characterized by a cyclopenta[b]benzofuran skeleton. In 1982 King and colleagues discovered the first member of this family, rocaglamide, based on its antileukemic activity. Since then, about 50 other flavaglines have been characterized. These molecules display strong insecticidal, antifungal, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities. In mouse models of cancer, flavaglines enhance the efficacy of chemotherapies and also alleviate the cardiac adverse effect of these chemotherapies.The challenge raised by their structural complexity has attracted the attention of some organic chemists. In 1990, Barry Trost presented an enantioselective synthesis of rocaglamide in 18 steps and confirmed its absolute configuration.GPAM
Glycerol-3-phosphate acyltransferase 1, mitochondrial is an enzyme that in humans is encoded by the GPAM gene.Glycerol-3-phosphate acyltransferase (GPAT; EC 220.127.116.11), which catalyzes the initial and committing step in glycerolipid biosynthesis, is predicted to play a pivotal role in the regulation of cellular triacylglycerol and phospholipid levels. Two mammalian forms of GPAT have been identified on the basis of localization to either the endoplasmic reticulum or mitochondria.[supplied by OMIM]IL2RA
Interleukin-2 receptor alpha chain (also called CD25) is a protein that in humans is encoded by the IL2RA gene.The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL2 receptor. Homodimeric alpha chains (IL2RA) result in low-affinity receptor, while homodimeric beta (IL2RB) chains produce a medium-affinity receptor. Normally an integral-membrane protein, soluble IL2RA has been isolated and determined to result from extracellular proteolysis. Alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is currently unknown.Immune tolerance
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in given organism. It is induced by prior exposure to that specific antigen and contrasts with conventional immune-mediated elimination of foreign antigens (see Immune response). Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced—in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). The mechanisms by which these forms of tolerance are established are distinct, but the resulting effect is similar.
Immune tolerance is important for normal physiology. Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.). Deficits in central or peripheral tolerance also cause autoimmune disease, resulting in syndromes such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, autoimmune polyendocrine syndrome type 1 (APS-1), and immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX), and potentially contribute to asthma, allergy, and inflammatory bowel disease. And immune tolerance in pregnancy is what allows a mother animal to gestate a genetically distinct offspring with an alloimmune response muted enough to prevent miscarriage.
Tolerance, however, also has its negative tradeoffs. It allows for some pathogenic microbes to successfully infect a host and avoid elimination. In addition, inducing peripheral tolerance in the local microenvironment is a common survival strategy for a number of tumors that prevents their elimination by the host immune system.KIR3DL1
Killer cell immunoglobulin-like receptor 3DL1 is a protein that in humans is encoded by the KIR3DL1 gene.Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte immunoglobulin-like receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response.Locus suicide recombination
Locus suicide recombination (LSR) constitutes a variant form of class switch recombination that eliminates all immunoglobulin heavy chain constant genes. It thus terminates immunoglobulin and B-cell receptor (BCR) expression in B-lymphocytes and results in B-cell death since survival of such cells requires BCR expression. This process is initiated by the enzyme activation-induced deaminase upon B-cell activation. LSR is thus one of the pathways that can result into activation-induced cell death in the B-cell lineage.Luk Van Parijs
Luk Van Parijs was an associate professor of biology at the Massachusetts Institute of Technology (MIT) Center for Cancer Research. After investigating for a year, MIT fired Van Parijs for research misconduct. Van Parijs admitted to fabricating and falsifying research data in a paper, several unpublished manuscripts, and grant applications. In March 2011, Van Parijs pleaded guilty in a U.S. District Court in Boston to one count of making a false statement on a federal grant application. The government asked Judge Denise Casper for a 6-month jail term because of the seriousness of the fraud, which involved a $2-million grant. After several prominent scientists including Van Parijs' former post-doc supervisor pleading for clemency on his behalf, on 13 June, Van Parijs was finally sentenced six months of home detention with electronic monitoring, plus 400 hours of community service and a payment to MIT of $61,117 - restitution for the already-spent grant money that MIT had to return to the National Institutes of Health .
Van Parijs' area of research was in the use of short-interference RNA in studying disease mechanisms, especially in autoimmune diseases. He was studying normal immune cell function and defects in these cells during disease development.RIPK3
Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that in humans is encoded by the RIPK3 gene.The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases, and 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 apoptosis and weakly activate the NF-kappaB transcription factor.SIVA1
Apoptosis regulatory protein Siva is a protein that in humans is encoded by the SIVA1 gene.
This gene encodes a protein with an important role in the apoptotic (programmed cell death) pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described.TSC22D3
TSC22 domain family protein 3 is a protein that in humans is encoded by the TSC22D3 gene.