A pyknosis inducing factor was identified as Acinus ('apoptotic chromatin condensation inducer in the nucleus'), which is the precursor of an active chromatin condensating factor. Acinus is cleaved by caspase-3 (Sahara et al, 1999, Nature, 401:168-172).
Activation Induced Cell Death; Apoptosis of active lymphocytes that have to be removed after an immune response. More...
Acquired ImmunoDeficiency Syndrome (AIDS) is a disease caused by infection with the Human Immunodeficiency Virus (HIV). The late symptomatic stage of AIDS is associated with a progressive decline in CD4+ T cell levels, impaired immune function and an increase in viral load. Systemic and focal symptoms of HIV infection, opportunistic infections and neoplasms may occur. Infection of CD4+ Tcells with HIV is associated with a cytopathic effect of the virus finally leading to cell-death by apoptosis of both infected and non-infected cells. More...
A form of cancer that develops from a malignant abnormality in the glandular cells lining an organ such as the prostate. Cancers of the prostate but also the breast and the pancreas are usually adenocarcinomas.
Apoptosis Inducing Factor, a 57 kDa flavoprotein with homology to bacterial oxidoreductases. AIF is located in the mitochondria but it translocates to the nucleus when apoptosis is induced. AIF induces chromatin condensation in isolated nuclei and large-scale fragmentation of DNA; AIF also induces dissipation of the mitochondrial transmembrane potential and exposure of phosphatidylserine in the plasma membrane. It induces purified mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Bcl-2 can prevent the release of AIF from the mitochondrion but does not affect its apoptogenic activity (Susin et al, 1999, Nature, 397: 441-446). More...
Akt is a serine-threonine kinase that is implicated in apoptosis suppression induced by Ras, growth factor receptors, neurotrophin receptors and oncogenes. Akt phosphorylates and therfore inactivates pro-Caspase-9 and Bad. Akt itself is activated by the PI3K second messenger.
Autoimmune LymphoProliferative Syndrome; human inheritable disorder, manifesting in non-malignant lymphoproliferation and autoimmune symptoms caused by defective lymphocyte apoptosis. In Type Ia Autoimmune Lymphoproliferative Syndrome (type Ia ALPS) the CD95/FasR is defect, whereas in type Ib ALPS the CD95L/FasL is defect. The defect is frequently due to a mutation in the Death Domain of CD95. Since this genetic defect is heterozygous, and since parents are physically unaffected, a secondary, as yet unknown, defect must exist that is responsible for the symptoms.
Angelman Syndrome (AS) is characterized by microcephaly, severe mental retardation, ataxic gate, hyperactivity and seizures. AS result from a lack of a maternal contribution to the imprinted chromosome 15q11-q13 region. A candidate AS gene, ubiquitin protein ligase 3A (UBE3A/E6-AP), has been identified,and mutations of this gene have been detected in several cases of AS. Prader-Willi syndrome (PWS) also maps to chromosome 15q11-q13, but displays the opposite pattern of inheritance.
Anoikis is the term for detachment-induced cell death: cells undergo apoptosis upon disruption of the cell-matrix interactions. Involved are interactions between integrins and proteins of the extracellular matrix, as well as RGD peptides.
As has been studied in erythrocytes, the polypeptide ankyrin binds both to transmembrane proteins and to spectrin, and by this links the plasma membrane to the cytoskeleton. Repeats of homologous ankyrin sequences have been found in all IkB family members. It is the interaction between ankyrin repeats of IkB and regions of the RHD of Rel/NF-kB proteins that prevents nuclear translocation of Rel/NF-kB protein dimers.
Adenine Nucleotide Translocator, a member of the PT pore in the inner mitochondrial membrane. There are two highly homologous isoforms of ANT, ANT-1 and ANT-2. Interestingly, Ant-1 induces apoptosis when overexpressed, whereas ANT-2 does not (Bauer et al., 1999, J Cell Biol; 147(7):1493-502).
Apoptotic Protease Activating Factor 1: Mammalian CED-4 homolog. In the presence of cytosolic cytochrome c, released from the mitochondria during apoptosis-induction, Apaf-1 forms the apoptosome, a multimeric complex consisting of Apaf-1, cyto c, dATP/ATP and procaspase-9. In this complex, procaspase-9 is processed to active caspase-9 by autocatalysis. Recently, several Apaf-1-like genes have been identified in vertebrates (Cecconi, 1999, Cell Death Diff., 6: 1087-98). The proteins encoded by these genes contain distinct amino- and carboxy-terminal sequences, suggesting that they may interact with and activate other caspases than Apaf-1 through different upstream signaling pathways.More...
Apoptotic Protease Activating Factors. More...
Acute Promyelocytic Leukemia
The term 'apoptosis' describes the molecular and morphological processes leading to controlled cellular self-destruction. Frequently, the terms 'apoptosis' and 'programmed cell death' are used as synonyms.
For more see a short description or go directly to a more detailed introduction to apoptotic cell death: ApoReview - Introduction to Apoptosis!
The apoptosome is a multimeric complex consisting of Apaf-1, cyto c, dATP/ATP and procaspase-9. In this complex, procaspase-9 is processed to active caspase-9 by autocatalysis. More...
Alternative Reading Frame (also called p14ARF within the p16INK4A locus. ARF is a tumor suppressor which regulates p53 stability, possibly by interacting with p53 and MDM2. More...
Apoptosis Related Killer (Ark), also known as Dark, dapaf-1 or hac-1.
Apoptosis-associated Speck-like protein containing a CARD (ASC) was identified as a cytosolic protein that forms speck-like aggregates within the cell after induction of apoptosis (Masumoto et al., 1999, JBC, 274(48):33835-33838). ASC contains a N-terminal PAAD domain and a C-terminal CARD domain. The ASC CARD domain was reported to specifically associate with the CARD domain of the CARD12 protein (Geddes et al., 2001, Biochem Biophys Res Commun, 284(1):77-82) and to activate caspase-1 via CARD-CARD interactions (Srinivasula et al., 2002, JBC, April). The PAAD domain is suspected to interfere with activation of NF-kB by inhibiting IKK activity and by inhibiting IkB-alpha degradation following TNF stimulation. Indeed, IKKs colocalize to filaments formed by the ASC PAAD domains. High levels of ASC are abundantly expressed in epithelial cells and leukocytes, which are involved in host defense against external pathogens and in well-differentiated cells.
Apoptosis Signal Regulating Kinase 1; ASK1 is a MAP3k which leads to JNK activation; ASK1 interacts with DAXX. More...
Apoptosis-Stimulating Protein for p53, ASPP, is a family of proteins interacting with p53 and thereby specifically enhancing p53-induced apoptosis but not cell cycle arrest. The ASPP family consists of the members ASPP1 and ASPP2. The name ASPP also was supposed to emphasize the structural features of those proteins including Ankyrin repeats, a SH3 domain, and Proline-rich domains. The ASPPs directly interact with p53, and specifically enhance the apoptotic function of p53 by stimulting its DNA binding and transactivation function on promoters of proapoptotic genes such as Bax and PIG-3 but not of cell cycle arrest genes such as p21. Interestingly, expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP might regulate the tumor suppression function of p53 in vivo (Samuels-Lev et al, 2001, Mol. Cell, 8: 781-794).
ATM is the gene mutated in ataxia-telangiectasia (AT) patients. AT is an autosomal recessive disease characterized by high cancer predisposition, radiation sensitivity, increased chromosome breakage, and other physiological symptoms. Cells from AT patients show reduced and delayed accumulation of p53 protein and its transactivational activity in response to ionizing radiation. ATM is one of the major upstream regulators of the p53 response to radiation-induced damage, possibly by regulating the phosphorylation status of p53.
There are ATP-dependent steps in the apoptotic process, and it was reported that ATP levels might determine the cell death fate by apoptosis or necrosis (Eguchi et al., 1997, Cancer Res., 57: 1835-40). Known ATP-dependent steps are the activation of caspase-9 by Apaf-1/cyto c and more downstream the active nuclear transport mechanism (Eguchi et al., 1999, Cancer Res., 59: 2174-81).
Aven is a strong antiapoptotic modulator of the apoptosome complex by preventing homodimerization of Apaf-1 (Chau et al., 2000, Mol. Cell, 6: 31-40)
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