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Integrated Stress Response
The integrated stress response is a cellular stress response evolutionary conservation, conserved in eukaryotic cell (biology), cells that downregulates protein synthesis and upregulates specific genes in response to internal or environmental stresses. Background The integrated stress response can be triggered within a cell due to either extrinsic or intrinsic conditions. Extrinsic factors include Hypoxia (medical), hypoxia, amino acid deprivation, glucose deprivation, viral infection and presence of oxidants. The main intrinsic factor is endoplasmic reticulum stress due to the accumulation of protein folding, unfolded proteins. It has also been observed that the integrated stress response may trigger due to oncogene activation. The integrated stress response will either cause the gene expression, expression of genes that fix the damage in the cell due to the stressful conditions, or it will cause a cascade of events leading to apoptosis, which occurs when the cell cannot be bro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cellular Stress Response
Cellular stress response is the wide range of molecular changes that cells undergo in response to environmental stressors, including extremes of temperature, exposure to toxins, and mechanical damage. Cellular stress responses can also be caused by some viral infections. The various processes involved in cellular stress responses serve the adaptive purpose of protecting a cell against unfavorable environmental conditions, both through short term mechanisms that minimize acute damage to the cell's overall integrity, and through longer term mechanisms which provide the cell a measure of resiliency against similar adverse conditions. General characteristics Cellular stress responses are primarily mediated through what are classified as ''stress proteins''. Stress proteins often are further subdivided into two general categories: those that only are activated by stress, or those that are involved both in stress responses and in normal cellular functioning. The essential character of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein ( substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets and most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction. Chemical ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2AK2
Protein kinase RNA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is an enzyme that in humans is encoded by the ''EIF2AK2'' gene. PKR protects against viral infections. Mechanism of action Protein kinase-R is activated by double-stranded RNA (dsRNA), introduced to the cells by a viral infection. PKR can also be activated by the protein PRKRA, PACT or by heparin. PKR contains an N-terminal dsRNA binding domain (dsRBD) and a C-terminal kinase domain, that gives it pro-apoptotic (cell-killing) functions. The dsRBD consists of two tandem copies of a conserved double stranded RNA binding motif, dsRBM1 and dsRBM2. PKR is induced by interferon in a latent state. Binding to dsRNA is believed to activate PKR by inducing protein dimerization, dimerization and subsequent auto-phosphorylation reactions. In situations of viral infection, the dsRNA create ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2AK4
Eukaryotic translation initiation factor 2-alpha kinase 4 is an enzyme that in humans is encoded by the ''EIF2AK4'' gene. EIF2AK4 belongs to a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2S1; MIM 603907) to downregulate protein synthesis in response to varied cellular stresses (Berlanga et al., 1999). upplied by OMIMref name="entrez"/> See also * Gcn2 GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that senses amino acid deficiency through binding to uncharged transfer RNA (tRNA). It plays a key role in modulating amino acid metabolism as a response to nutrient d ... References Further reading * * * * * * * * External links * EC 2.7.11 {{gene-15-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2AK1
Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the ''EIF2AK1'' gene. Function EIF2AK1 inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. EIF2AK1 exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Owing to this unique heme-sensing capacity, it plays a crucial role in shutting off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), it controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of the heme and globin moieties of hemoglobin. Thus plays an essential protective role for ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2AK3
Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the ''EIF2AK3'' gene. Function The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by proteopathy, malfolded proteins. Clinical significance Patients with mutations in this gene develop Wolcott-Rallison syndrome. Interactions EIF2AK3 has been shown to Protein-protein interaction, interact with DNAJC3, NFE2L2, and endoplasmic reticulum chaperone BiP (Hsp70). Inhibitors * GSK2606414 * 3-Fluoro-GSK2606414 References Further reading * * * * * * * * * * * * * * * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mammalian
Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or hair, and three ossicles, middle ear bones. These characteristics distinguish them from reptiles (including birds) from which they Genetic divergence, diverged in the Carboniferous, over 300 million years ago. Around 6,400 extant taxon, extant species of mammals have been described divided into 29 Order (biology), orders. The largest Order (biology), orders, in terms of number of species, are the rodents, bats, and Eulipotyphla (hedgehogs, Mole (animal), moles, shrews, and others). The next three are the Primates (including humans, apes, monkeys, and others), the Artiodactyla (cetaceans and even-toed ungulates), and the Carnivora (cats, dogs, pinniped, seals, and others). In terms of cladistic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2γ
Eukaryotic translation initiation factor 2 subunit 3 (eIF2γ) is a protein that in humans is encoded by the ''EIF2S3'' gene. Function Eukaryotic translation initiation factor 2 (eIF2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. eIF2 is composed of three subunits, alpha (α), beta (β), and gamma (γ, this article), with the protein encoded by this gene representing the gamma subunit. See also * eIF2 Eukaryotic Initiation Factor 2 (eIF2) is an eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer c ... References Further reading * * * * * * * * * * * * * * * * * {{gene-X-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2β
Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the ''EIF2S2'' gene. Function Eukaryotic translation initiation factor 2 (eIF2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. eIF2 is composed of three subunits, alpha (α), beta (β, this article), and gamma (γ), with the protein encoded by this gene representing the beta subunit. The beta subunit catalyzes the exchange of GDP for GTP, which recycles the eIF2 complex for another round of initiation. Regulation Both eIF2α and eIF2β expression is regulated by the NRF1 transcription factor. See also * eIF2 Eukaryotic Initiation Factor 2 (eIF2) is an eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer c ... References F ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2α
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ATF4
Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ''ATF4'' gene. Function This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 ( CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein–protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA-binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EIF2
Eukaryotic Initiation Factor 2 (eIF2) is an eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer consisting of an alpha (also called subunit 1, EIF2S1), a beta (subunit 2, EIF2S2), and a gamma (subunit 3, EIF2S3) subunit. Once the initiation phase has completed, eIF2 is released from the ribosome bound to GDP as an inactive binary complex. To participate in another round of translation initiation, this GDP must be exchanged for GTP. Function eIF2 is an essential factor for protein synthesis that forms a ternary complex (TC) with GTP and the initiator Met-tRNAiMet. After its formation, the TC binds the 40S ribosomal subunit to form the 43S preinitiation complex (43S PIC). 43S PIC assembly is believed to be stimulated by the initiation factors eIF1, eIF1A, and the eIF3 complex according to ''in vitro'' experiments. The 43S PIC then ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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