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HDAC Inhibitor
Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. Since deacetylation of histones produces transcriptionally silenced heterochromatin, HDIs can render chromatin more transcriptionally active and induce epigenomic changes. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics, such as valproic acid. Since at least 2003 they have been investigated as possible treatments for cancers, parasitic and inflammatory diseases. Cellular biochemistry/pharmacology To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetyl transferases (HAT), which acetylate the lysine residues in core histones leading to a less compact and more transcriptionally active euchromatin, and, on the converse, the actions of histone deacetylases (HDAC), which remove the acetyl groups from the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme Inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its Enzyme activity, activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which Substrate (biochemistry), substrate molecules are converted into Product (chemistry), products. An enzyme Enzyme catalysis, facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the Rate-determining step, most difficult step of the reaction. An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's catalysis of the reaction is blocked. Enzyme inhibitors may bind Reversible reaction, reversibly or irreversibly. Irreversible inhibitors form a Covalent bond, chemical bond with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By cont ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Estrogen Receptor Alpha
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ''ESR1'' (EStrogen Receptor 1). Structure The estrogen receptor (ER) is a ligand (biochemistry), ligand-activated transcription factor composed of several protein domain, domains important for hormone binding, DNA-binding domain, DNA binding, and activator (genetics), activation of transcription (genetics), transcription. Alternative splicing results in several ESR1 messenger RNA, mRNA transcripts, which differ primarily in their five prime untranslated region, 5-prime untranslated regions. The translated receptors show less variability. Ligands Agonists Non-selective * Endogenous estrogens (e.g., estradiol, estrone, estriol, estetrol) * Natural product, Natural estrogens (e.g. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC11
Histone deacetylase 11 is a 39kDa histone deacetylase enzyme that in humans is encoded by the ''HDAC11'' gene on chromosome 3 in humans and chromosome 6 in mice. It is the only Class IV HDAC since it is not highly homologous with either Rpd3 or hda1 yeast enzymes and so does not fit into either Class I or Class II. It is the smallest HDAC isoform and it was first described in 2002. Function Histone deacetylases, such as HDAC11, control DNA expression by modifying the core histone octamers that package DNA into dense chromatin structures and repress gene expression. upplied by OMIMref name="entrez" /> HDAC11 expression is normally found in brain and testis tissue, but upregulation of HDAC11 expression has also been seen in various cancer cells. HDAC11 has been shown to be a negative regulator of IL-10 production in antigen presenting cells. It has also been shown that inhibition of HDAC11 results in increased expression of OX40L in Hodgkin lymphoma cells. Interactions HDA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sirtuins
Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins that possess either mono- ADP-ribosyltransferase or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2', the gene responsible for cellular regulation in yeast. From ''in vitro'' studies, sirtuins were thought to be implicated in influencing cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy efficiency and alertness during low-calorie situations. As of 2018, there was no clinical evidence that sirtuins affect human aging, and a 2022 review criticized researchers who propagate this claim. Yeast Sir2 and some, but not all, sirtu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC10
Histone deacetylase 10 is an enzyme that in humans is encoded by the ''HDAC10'' gene. HDAC10 is a class IIb HDAC. It specifically has selectivity for long, slender polyamines like N8-acetylspermidine. Acetylation of histone core particles modulates chromatin structure and gene expression. The opposing enzymatic activities of histone acetyltransferases and histone deacetylases, such as HDAC10, determine the acetylation status of histone tails (Kao et al., 2002). upplied by OMIMref name="entrez" /> Interactions HDAC10 has been shown to interact with Histone deacetylase 2 and Nuclear receptor co-repressor 2. See also * Histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important becaus ... References Further reading * * * * * * * * External links * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC6
Histone deacetylase 6 is an enzyme that in humans is encoded by the ''HDAC6'' gene. HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains that appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription. It retracts the cilium of the cell, which is necessary prior to mitosis. * HDAC encourages cell motility and catalyzes α-tubulin deacetylation. As a result the enzyme encourages cancer cell metastasis. HDAC6 affects transcription and tr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC9
Histone deacetylase 9 is an enzyme that in humans is encoded by the ''HDAC9'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. H ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC5
Histone deacetylase 5 is an enzyme that in humans is encoded by the ''HDAC5'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene. AMP-activated protein kinase regulation of the glucose transporter GLUT4 occurs by phosphorylation of HDAC5. HDAC5 is involved in memor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC4
Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the ''HDAC4'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation. Clinical significance Studies have shown that HDAC4 regulates bone and muscle development. Harvard University researchers also concluded that it promotes healthy vision: Reduced levels of the protein led to the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC8
Histone deacetylase 8 is an enzyme that in humans is encoded by the ''HDAC8'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation / deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. Histone deacetylase 8 is involved in skull morphogenesis and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex. Clinical significance HDAC8 has been linked to number of disease states notably to acute myeloid leukemia and is related to actin cytoskeleton in smooth muscle cells. siRNA targeting HDAC8 showed anticancer effects. Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas. In addition the HDAC8 enzyme has been implicated in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC3
Histone deacetylase 3 is an enzyme encoded by the ''HDAC3'' gene in both humans and mice. Function Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein component of chromatin. The posttranslational and enzymatically mediated Histone acetylation and deacetylation, lysine acetylation and deacetylation of histone tails change the local chromatin structure by altering the electrostatic attraction between the negatively charged DNA backbone and histones. HDAC3 is a Class I member of the Histone deacetylase#HDAC super family, histone deacetylase superfamily (comprising Histone deacetylase#Classes of HDACs in higher eukaryotes, four classes based on function and DNA sequence homology) that is recruited to enhancers to modulate both the epigenome and nearby gene expression. HDAC3 is found exclusively in the Histone deacetylase#Classes of HDACs in higher eukaryotes, cell nucleus, where it is the sole e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC2
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones (H2A, H2B, H3, and H4). As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy. Though the functional role of the class to which HDAC2 belongs has been carefully studied, the mechanism by which HDAC2 interacts with histone deacetylases of other classes has yet to be elucidated. HDAC2 is broadly regulated by protein kinase 2 (CK2) and protein phosphatase 1 (PP1), but biochemical analysis suggests its regulation is more complex (evinced by the coexistence of HDAC1 and HDAC2 in three distinct protein complexes). Essentially, the mechanism by which HDAC2 is regulated is still unclear ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
