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MED1
Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the ''MED1'' gene. MED1 functions as a nuclear receptor coactivator. Function The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes .g., thyroid hormone receptor-(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53-dependent ap ...
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Mediator Complex
Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered in 1990 in the lab of Roger D. Kornberg, recipient of the 2006 Nobel Prize in Chemistry. Mediator complexes interact with transcription factors and RNA polymerase II. The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase. Mediator complexes are variable at the evolutionary, compositional and conformational levels. The first image shows only one "snapshot" of what a particular mediator complex might be composed of, but it certainly does not accurately depict the conformation of the complex ''in vivo''. During evolution, mediator has become more complex. The yeast ''Saccharomyces cerevisiae'' (a simple eukaryote) is thought to have up to 21 subunits in the core mediator (exclusive of the CDK module), while mammals have up to 26. Individual subunits can be absent or replaced by other subunits under differe ...
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Cyclin-dependent Kinase 8
Cell division protein kinase 8 is an enzyme that in humans is encoded by the ''CDK8'' gene. Function The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. CDK8 binds to and/or phosphorylates several transcription factors, which can have an activating or inhibitory effect on transcription factor function. CDK8 phosphorylates the Notch intracellular domain, SREBP, and STAT1 S727. CDK8 also inhibits transcriptional activation by influencing turnover of subunits in the mediator complex tail module. In addition, CDK8 influences binding of RNA polymerase II to the mediator complex. Clinical significance CDK8 is a colorectal cancer oncogene: the ''CDK8'' gene is amplified in human colorectal tumors, activating β-catenin-mediated transcription that drives colon tumorigenesis. However, CDK8 may not be oncogenic in all cell types, and ...
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PPARGC1A
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a protein that in humans is encoded by the ''PPARGC1A'' gene. PPARGC1A is also known as human accelerated region 20 ( HAR20). It may, therefore, have played a key role in differentiating humans from apes. PGC-1α is the master regulator of mitochondrial biogenesis. PGC-1α is also the primary regulator of liver gluconeogenesis, inducing increased gene expression for gluconeogenesis. Function PGC-1α is a super strong gene that contains two promoters, and has 4 alternative splicings. PGC-1α is a transcriptional coactivator that regulates the genes involved in energy metabolism. It is the master regulator of mitochondrial biogenesis. This protein interacts with the nuclear receptor PPAR-γ, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activity of, cAMP response element-binding protein (CREB) and nuclear respir ...
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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-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability. Ligands Agonists Non-selective * Endogenous estrogens (e.g., estradiol, estrone, estriol, estetrol) * Natural estrogens (e.g., conjugated equine estrogens) * Synthetic estrogens (e.g., ethinylestradiol, diethylstilbestrol) Selective Agonists of ERα selective over ERβ include: * Propylp ...
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Thyroid Hormone Receptor Alpha
Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the ''THRA'' gene. Function The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Alternatively spliced transcript variants encoding distinct isoforms have been reported. Role in pathology Mutations of the THRA gene may cause nongoitrous congenital hypothyroidism-6, a subtype of congenital hypothyroidism. Interactions THR1 has been shown to interact with: * COPS2, * EP300, * ITGB3BP, * MED1, * MED6, * MED12, * MED16, * MEF2A, * NCOA6, * TRIP11, and * UBC The University of B ...
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BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA. ''BRCA1'' and '' BRCA2'' are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks. If ''BRCA1'' or ''BRCA2'' itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. ''BRCA1'' and ''BRCA2'' have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal, ...
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Hepatocyte Nuclear Factor 4 Alpha
Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the ''HNF4A'' gene. Function HNF-4α is a nuclear transcription factor that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene plays a role in development of the liver, kidney, and intestines. Alternative splicing of this gene results in multiple transcript variants. HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4. Genetic mutations in the ''HNF4A'' gene can influence the activity of HNF4α's downstream proteins such as CYP2D6, ''in vitro'' and ''in vivo''. The alkaloid berberine upregulates the expression of HNF4A. This gene also plays a pivotal role in the expression and synthesis of SHBG, an important glyc ...
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Glucocorticoid Receptor
The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates genes controlling the development, metabolism, and immune response. Because the receptor gene is expressed in several forms, it has many different (pleiotropic) effects in different parts of the body. When glucocorticoids bind to GR, its primary mechanism of action is the regulation of gene transcription. ree full text/ref> The unbound receptor resides in the cytosol of the cell. After the receptor is bound to glucocorticoid, the receptor-glucocorticoid complex can take either of two paths. The activated GR complex up-regulates the expression of anti-inflammatory proteins in the nucleus or represses the expression of pro-inflammatory proteins in the cytosol (by preventing the translocation of other transcription factors from the cytosol ...
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Calcitriol Receptor
The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the ''VDR'' gene located on chromosome 12q13.11. VDR is expressed in most tissues of the body, and regulates transcription of genes involved in intestinal and renal transport of calcium and other minerals. Glucocorticoids decrease VDR expression. Many types of immune cells also express VDR. Function The VDR gene encodes the nuclear hormone receptor for vitamin D. The most potent natural ...
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TGS1
Trimethylguanosine synthase is an enzyme that in humans is encoded by the ''TGS1'' gene. Interactions TGS1 has been shown to interact with: * CREB-binding protein, and * EED, * EP300, * MED1, and * NCOA6 Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene. Function The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcrip .... References Further reading

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Peroxisome Proliferator-activated Receptor Gamma
Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the ''PPARG'' gene. Tissue distribution PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine). Gene expression This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte di ...
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Androgen Receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor. The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression; however, the androgen receptor has other functions as well. Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype. Function Effect on development In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. T ...
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