Stress Granule
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Stress Granule
Stress granules are dense aggregations in the cytosol composed of proteins and RNAs that appear when the cell is under stress. The RNA molecules stored are stalled translation pre-initiation complexes: failed attempts to make protein from mRNA. Stress granules are 100–200 nm in size (when biochemically purified), not surrounded by membrane, and associated with the endoplasmatic reticulum. Note that there are also nuclear stress granules. This article is about the cytosolic variety. Proposed functions The function of stress granules remains largely unknown. Stress granules have long been proposed to have a function to protect RNAs from harmful conditions, thus their appearance under stress. The accumulation of RNAs into dense globules could keep them from reacting with harmful chemicals and safeguard the information coded in their RNA sequence. Stress granules might also function as a decision point for untranslated mRNAs. Molecules can go down one of three paths: further ...
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Stress Granule Dynamics
Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase or sentence * Stress (mechanics), the internal forces that neighboring particles of a continuous material exert on each other * Occupational stress, stress related to one's job * Psychological stress, a feeling of strain and pressure * Surgical stress, systemic response to surgical injury Arts, entertainment, and media Music Groups and musicians * Stress (Brazilian band), a Brazilian heavy metal band * Stress (British band), a British rock band * Stress (pop rock band), an early 1980s melodic rock band from San Diego * Stress (musician) (born 1977), hip hop singer from Switzerland * Stress (record producer) (born 1979), artistic name of Can Canatan, Swedish musician and record producer Albums * ''Stress'' (Anonymus album), 1997 * ''St ...
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Thapsigargin
Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). Structurally, thapsigargin is classified as a guaianolide, and is extracted from a plant, ''Thapsia garganica''. It is a tumor promoter in mammalian cells. Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. Store-depletion can secondarily activate plasma membrane calcium channels, allowing an influx of calcium into the cytosol. Depletion of ER calcium stores leads to ER stress and activation of the unfolded protein response. Non-resolved ER stress can cumulatively lead to cell death. Prolonged store depletion can protect against ferroptosis via remodeling of ER-synthesized phospholipids. Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. Thapsigargin is useful in experimentation examining the impacts of incre ...
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TIA-1
TIA1 or Tia1 cytotoxic granule-associated rna binding protein is a 3'UTR mRNA binding protein that can bind the 5'TOP sequence of 5'TOP mRNAs. It is associated with programmed cell death (apoptosis) and regulates alternative splicing of the gene encoding the Fas receptor, an apoptosis-promoting protein. Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called stress granules. It is encoded by the TIA1 gene. Mutations in the ''TIA1'' gene have been associated with amyotrophic lateral sclerosis, frontotemporal dementia, and Welander distal myopathy. It also plays a crucial role in the development of toxic oligomeric tau in Alzheimer's disease. Function This protein is a member of a RNA-binding protein family that regulates transcription and RNA translation. It was first identified in cytotoxic lymphocyte (CTL) target cells. TIA1 acts in the nucleus to regulate splicing and transcription. TIA1 helps to recruit the splicesome to regulate RNA splicin ...
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Prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It is not known what causes a normal protein to misfold, but the resulting abnormal three-dimensional structure confers infectious properties by collapsing nearby protein molecules into the same shape. The word ''prion'' is derived from the term, "proteinaceous infectious particle". In comparison to all other known infectious agents such as viroids, viruses, bacteria, fungi, and parasites, all of which contain nucleic acids ( DNA, RNA, or both), the hypothesized role of a protein as an infectious agent stands in contrast. Prion isoforms of the prion protein (PrP), whose specific function is uncertain, are hypothesized as the cause of transmissible spongiform encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) ...
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EIF2S1
Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the ''EIF2S1'' gene. Function The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 protein complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNAiMet) to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article), beta (β, 38 kD), and gamma (γ, 52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2α. Phosphorylation of eIF2α by EIF-2 kinases plays a key role in regulating the integrated stress response. Clinical significance After reperfusion following brain ischemia, there is inhibition of neuron protein synthesis due to phosphorylation of eIF2α. There is colocalization between phos ...
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Eukaryotic Initiation Factor
Eukaryotic initiation factors (eIFs) are Protein, proteins or Protein complex, protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for Post-transcriptional regulation, post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNAiMet called the 43S preinitiation complex (43S PIC). Additional factors of the eIF4F complex (eIF4A, E, and G) recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex (48S PIC), followed by large 60S ribosomal subunit recruitment to form the Eukaryotic ribosome (80S), 80S ribosome. There exist many more eukaryotic ini ...
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Phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. Glucose Phosphorylation of sugars is often the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by :D-glucose + ATP → D-glucose-6-phosphate + ADP : ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition) Hepatic cells are freely permeable to glucose, and ...
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Kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups (dephosphorylation). The phosphorylation state of a molecule, whet ...
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Puromycin
Puromycin is an antibiotic protein synthesis inhibitor which causes premature chain termination during translation. Inhibition of translation Puromycin is an aminonucleoside antibiotic, derived from the '' Streptomyces alboniger'' bacterium, that causes premature chain termination during translation taking place in the ribosome. Part of the molecule resembles the 3' end of the aminoacylated tRNA. It enters the A site and transfers to the growing chain, causing the formation of a puromycylated nascent chain and premature chain release. The exact mechanism of action is unknown at this time but the 3' position contains an amide linkage instead of the normal ester linkage of tRNA. That makes the molecule much more resistant to hydrolysis and stops the ribosome. Puromycin is selective for either prokaryotes or eukaryotes. Also of note, puromycin is critical in mRNA display. In this reaction, a puromycin molecule is chemically attached to the end of an mRNA template, which is then ...
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Rocaglamide
Rocaglamide is a natural product which belongs to a class of molecules called flavaglines. This compound was isolated in 1982 by King, Ming-Lu (金明儒) and colleagues based on its antileukemic activity. The name of Rocaglamide is named from two parts: Roc- and aglamide. Roc- means Republic of China(中華民國), the place in which this product isolated; aglamide indicates this product is isolated from Large-leaved Aglaia (Scientific name: Aglaia rimosa Rocaglamide was first synthesized by Barry Trost in 1990. Although other syntheses have been described since, Trost’s remains the only one to afford rocaglamide in an enantio-specific manner. See also * FL3 (flavagline) *Eukaryotic translation *eIF4A *Silvestrol Silvestrol is a natural product from the flavagline family, with a cyclopenta enzofuran core structure and an unusual dioxane ether side chain, which is found in the bark of trees from the genus ''Aglaia'', especially '' Aglaia silvestris'' and ' ... References ...
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Hippuristanol
Hippuristanol is a small molecule found in the coral ''Isis hippuris'' which was discovered by Jerry Pelletier and others of McGill University in Montreal, Quebec, Canada. It appears to have anti-viral activity and may hold promise as a cancer therapy.Compound from Coral Could Combat Cancer
''Scientific American'' March 13, 2006 Binds to and inhibits the eukaryotic protein .


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EIF4A
The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA. Background The mechanisms governing the basic subsistence of eukaryotic cells are immensely complex; it is therefore unsurprising that regulation occurs at a number of stages of protein synthesis – the regulation of translation has become a well-studied field. Human translational control is of increasing research interest as it has connotations in a range of diseases. Orthologs of many of the factors involved in human translation are shared by a range of eukaryotic organisms; some of which are used as model systems for the investigation of translation initiation and elongation, for example: sea urchin eggs upon fertilization, rodent brain and rabbit reticulocytes. Monod and Jacob were among the f ...
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