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Bcl-xL
B-cell lymphoma-extra large (Bcl-xL), encoded by the BCL2-like 1 gene, is a transmembrane molecule in the mitochondria. It is a member of the Bcl-2 family of proteins, and acts as an anti-apoptotic protein by preventing the release of mitochondrial contents such as cytochrome c, which leads to caspase activation and ultimately, programmed cell death. Function It is a well-established concept in the field of apoptosis that relative amounts of pro- and anti-survival Bcl-2 family of proteins determine whether the cell will undergo cell death; if more Bcl-xL is present, then pores are non-permeable to pro-apoptotic molecules and the cell survives. However, if Bax and Bak become activated, and Bcl-xL is sequestered away by gatekeeper BH3-only factors (e.g. Bim) causing a pore to form, cytochrome c is released leading to initiation of caspase cascade and apoptotic events. While the exact signaling pathway of Bcl-xL is still not known, it is believed that Bcl-xL differs highly fr ...
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BCL2-like 1 (gene)
Bcl-2-like protein 1 is a protein encoded in humans by the ''BCL2L1'' gene. Through alternative splicing, the gene encodes both of the human proteins Bcl-xL and Bcl-xS. Function The protein encoded by this gene belongs to the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act as anti- or pro- apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel ( voltage-dependent anion channels (VDACs) opening. VDACs regulate mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported. The longer isoform ( Bcl-xL) acts as an apoptotic inhibitor and the sho ...
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Bcl-2
Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first apoptosis regulator identified in any organism. Bcl-2 derives its name from ''B-cell lymphoma 2'', as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. Orthologs (such as ''Bcl2'' in mice) have been identified in numerous mammals for which complete genome data are available. Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma. Isoforms The two isoforms of Bcl-2, Isoform 1, and Isoform 2, exhibit a similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, sugge ...
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Bcl-2 Family
The Bcl-2 family (TC# 1.A.21) consists of a number of Conserved sequence, evolutionarily-conserved proteins that share Bcl-2 Sequence homology, homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. The Bcl-2 family proteins consists of members that either promote or inhibit apoptosis, and control apoptosis by governing mitochondrial outer membrane permeabilization (MOMP), which is a key step in the intrinsic pathway of apoptosis. A total of 25 genes in the Bcl-2 family were identified by 2008. Members of the BCL-2 family regulate apoptosis in mammals, reptiles, amphibs, fish, and other phyla of metazoan life, with exception of nematodes and insects. Their molecular structure and function, as well as their protein dynamics, are highly conserved over hundreds of millions of years in tissue forming life forms. Structure Bcl-2 family proteins have a general structure that consists of a Hydr ...
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Mcl-1
Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the ''MCL1'' gene. Function The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. The longer gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene product (isoform 2) promotes apoptosis and is death-inducing. The protein MCL1 has a very short biological half-life of only 20–30 minutes. The loss of MCL1 has a more dramatic impact than the loss of any other anti-apoptotic member of the Bcl-2 family. Loss of the ''Mcl-1'' gene results in embryo death when the embryo is only around 3.5 days old, before it has even implanted. Conditional deletion of ''Mcl-1'' depletes a wide variety of cells, including hematopoietic stem cells, B cell–committed progenitors, T cell–committed progenitors, ...
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Bcl-w
Bcl-2-like protein 2 is a 193-amino acid protein that in humans is encoded by the ''BCL2L2'' gene on chromosome 14 ( band q11.2-q12). It was originally discovered by Leonie Gibson, Suzanne Cory and colleagues at the Walter and Eliza Hall Institute of Medical Research, who called it Bcl-w. Function This gene encodes a pro-survival (anti-apoptotic) member of the bcl-2 protein family, and is most similar to Bcl-xL. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis. Clinical significance High levels of Bcl-w are seen in many cancers, including glioblastoma, colorectal cancer, non-small-cell lung carcinoma, ...
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Bcl-2 Homologous Antagonist Killer
Bcl-2 homologous antagonist/killer is a protein which in humans is encoded by the ''BAK1'' gene on chromosome 6. It belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. Structure BAK1 is a pro-apoptotic Bcl-2 protein containing four Bcl-2 homology (BH) domains: BH1, BH2, BH3, and BH4. These domains are composed of nine α-helices, with a hydrophobic α-helix core surrounded by amphipathic helices and a transmembrane C-terminal α-helix anchored to the mitochondrial outer membrane (MOM). A hydrophobic groov ...
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Senolytic
A senolytic (from the words ''senescence'' and ''-lytic'', "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases. Removal of senescent cells with senolytics has been proposed as a method of enhancing immunity during aging. A related concept is "senostatic", which means to suppress senescence. Research Possible senolytic agents are under preliminary research, including some which are in early-stage human trials. The majority of candidate senolytic compounds are repurposed anti-cancer molecules, such as the chemotherapeutic drug dasatinib and the experimental small molecule navitoclax. Soluble urokinase plasminogen activator surface receptor have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen ...
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TP53
p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence ''TP53''Gene nomenclature#Vertebrate gene and protein symbol conventions, ''italics'' are used to denote the ''TP53'' gene name and distinguish it from the protein it encodes is classified as a tumor suppressor gene. The ''TP53'' gene is the most frequently mutated gene (>50%) in human cancer, indicating that the ''TP53'' gene plays a crucial role in preventing cancer formation. ''TP53'' gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the ...
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Mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. The term ''mitochondrion'', meaning a thread-like granule, was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase popularized by Philip Siekevitz in a 1957 ''Scientific American'' article of the same name. Some cells in some multicellular organisms lack mitochondria (for example, mature mammalian red blood cells). The multicellular animal '' Henneguya salminicola'' is known to have retained mitochondrion-related organelles despite a complete loss of their mitochondrial genome. A large number of unicellular organisms, such as microspo ...
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Quercetin
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods. Occurrence Quercetin is a flavonoid widely distributed in nature. The name has been used since 1857, and is derived from ''quercetum'' (oak forest), after the oak genus ''Quercus''. It is a naturally occurring polar auxin transport inhibitor. Quercetin is one of the most abundant dietary flavonoids, with an average daily consumption of 25–50 mg. In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration. One study found that organically grown tomatoes had 79% more quercetin than non-organically grown fruit. Quercetin is present in ...
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Fisetin
Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It occurs in many plants where it serves as a yellow pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub .... It is found in many fruits and vegetables, such as strawberries, apples, persimmons, onions, and cucumbers. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891. Sources Fisetin is a flavonoid synthesized by many plants such as the trees and shrubs of Fabaceae, acacias '' Acacia greggii'', and '' Acacia berlandieri'', parrot tree ('' Butea frondosa''), honey locust ('' Gleditsia triacanthos''), members of the family Anacardiaceae such as the '' Quebracho colorado'', and species of the genus '' Rhus'', which contains the sumacs. Along wit ...
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