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HIF1A
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the ''HIF1A'' gene. The Nobel Prize in Physiology or Medicine 2019 was awarded for the discovery of HIF. HIF1A is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia. The dysregulation and overexpression of ''HIF1A'' by either hypoxia or genetic alternations have been heavily implicated in cancer biology, as well as a number of other pathophysiologies, specifically in areas of vascularization and angiogenesis, energy metabolism, cell survival, and tumor invasion. Two other alternative transcripts encoding different isoforms have been identified. Structure HIF1 is a heterodimeric basic helix-loop-helix structure that is composed of HIF1A, the alpha subunit (this protein), and the aryl hydrocarbon rece ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HIF-1
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex was discovered in 1995 by Gregg L. Semenza and postdoctoral fellow Guang Wang. In 2016, William Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza were presented the Lasker Award for their work in elucidating the role of HIF-1 in oxygen sensing and its role in surviving low oxygen conditions. In 2019, the same three individuals were jointly awarded the Nobel Prize in Physiology or Medicine for their work in elucidating how HIF senses and adapts cellular response to oxygen availability. Structure Most, if not all, oxygen-breathing species express the highly conserved transcriptional complex HIF-1, which is a heterodimer composed of an alpha and a beta subunit, the latter being a constitutively-expressed aryl hydrocarbon receptor nucl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aryl Hydrocarbon Receptor Nuclear Translocator
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with leukemia, acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene. The aryl hydrocarbon receptor (AhR) is involved in the induction of several enzymes that participate in xenobiotic metabolism. The ligand-free, cytosolic form of the aryl hydrocarbon receptor is complexed to Hsp90, heat shock protein 90. Binding of ligand, which includes dioxins and dioxin-like compounds, dioxin and polycyclic aromatic hydrocarbons, results in translocation of the ligand-binding subunit only into the nucle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transcription Factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome. TFs work alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prolyl Hydroxylase
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mechanism that requires alpha-Ketoglutaric acid, Fe2+, and ascorbate. This particular enzyme catalyzes the formation of (2''S'', 4''R'')-4-hydroxyproline, a compound that represents the most prevalent post-translational modification in the human proteome. Enzyme mechanism Procollagen-proline dioxygenase catalyzes the following reaction: L-proline + alpha-ketoglutaric acid + O2 → (2''S'', 4''R'')-4-hydroxyproline + succinate + CO2 The mechanism for the reaction is similar to that of other dioxygenases, and occurs in two distinct stages: In the first, a highly reactive Fe(IV)=O species is produced. Molecular oxygen is bound end-on in an axial position, producing a dioxygen unit. Nucleophilic attack on C2 generates a tetrahedral inte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Degradation
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, but may also occur by intra-molecular digestion. Proteolysis in organisms serves many purposes; for example, digestive enzymes break down proteins in food to provide amino acids for the organism, while proteolytic processing of a polypeptide chain after its synthesis may be necessary for the production of an active protein. It is also important in the regulation of some physiological and cellular processes including apoptosis, as well as preventing the accumulation of unwanted or misfolded proteins in cells. Consequently, abnormality in the regulation of proteolysis can cause disease. Proteolysis can also be used as an analytical tool for studying proteins in the laboratory, and it may also be used in industry, for example in food process ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell Proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation requires both cell growth and cell division to occur at the same time, such that the average size of cells remains constant in the population. Cell division can occur without cell growth, producing many progressively smaller cells (as in cleavage of the zygote), while cell growth can occur without cell division to produce a single larger cell (as in growth of neurons). Thus, cell proliferation is not synonymous with either cell growth or cell division, despite the fact that these terms are sometimes used interchangeably. Stem cells undergo cell proliferation to produce proliferating "transit amplifying" daughter cells that later differentiate to construct tissues during normal development and tissue growth, during tissue regeneration aft ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin.Sherwood, L, Klansman, H, Yancey, P: ''Animal Physiology'', Brooks/Cole, Cengage Learning, 2005. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells (erythrocytes). In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the liver. After seven months, erythropoiesis occurs in the bone marrow. Increased levels of physical ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. Low levels of EPO (around 10 mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Common causes of cellular hypoxia resulting in elevated levels of EPO (up to 10 000 mU/mL) include any anemia, and hypoxemia due to chronic lung disease. Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with the peritubular capillary and proximal convoluted tubule. It is also produced in perisinusoidal cells in the liver. Liver production predominates in the fetal and perinatal period; renal production predominates in adulthood. It is homologous with thrombopoietin. Exogenous erythropoietin, recombinant human erythropoietin (rhEPO), ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VEGF
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis (the '' de novo'' formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions. Serum concentration of VEGF is high in bronchial asthma and diabetes mellitus. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. It can contribute to disease. Sol ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetylation
: In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound. Organic synthesis Acetate esters and acetamides are generally prepared by acetylations. Acetylations are often used in making C-acetyl bonds in Friedel-Crafts reactions. Carbanions and their equivalents are susceptible to acetylations. Acetylation reagents Many acetylations are achieved using these three reagents: * Acetic anhydride. This reagent is common in the laboratory; its use cogenerates acetic acid. *Acetyl chloride. This reagent is also common in the laboratory, but its use cogenerates hydrogen chloride, which can be undesirable. *Ketene. At one time acetic anhydride was prepared by the reaction of ketene with acetic acid: :H2C=C=O + CH3COOH -> (CH3CO)2 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydroxylation
In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a molecule. The ''pattern of hydroxylation'' refers to the location of hydroxy groups on a molecule or material. Hydroxylation reactions Synthetic hydroxylations Installing hydroxyl groups into organic compounds can be effected by various metal catalysts. Many such catalysts are biomimetic, i.e. they are inspired by or intended to mimic enzymes such as cytochrome P450. Whereas many hydroxylations insert O atoms into bonds, some reactions ''add'' OH groups to unsaturated substrates. The Sharpless dihydroxylation is such a reaction: it converts alkenes into diols. The hydroxy groups are provided by hydrogen peroxide, which adds across the double bond of alkenes. Biological hydroxylation In biochemistry, hydroxylation reactions are often ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
