Tristetraprolin
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Tristetraprolin
Tristetraprolin (TTP), also known as zinc finger protein 36 homolog (ZFP36), is a protein that in humans, mice and rats is encoded by the ''ZFP36'' gene. It is a member of the TIS11 ( TPA-induced sequence) family, along with butyrate response factors 1 and 2. TTP binds to AU-rich elements (AREs) in the 3'-untranslated regions (UTRs) of the mRNAs of some cytokines and promotes their degradation. For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA. Mice deficient in TTP develop a complex syndrome of inflammatory diseases. Interactions ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH, and with NUP214, a member of the nuclear pore complex. Regulation Post-transcriptionally, TTP is regulated in several ways. The subcellular localization of TTP is influenced by interactions with protein partners such as the 14-3-3 family of proteins. These interactions and, possibly, intera ...
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Mir-29 MicroRNA Precursor
The miR-29 microRNA precursor, or pre-miRNA, is a small RNA molecule in the shape of a stem-loop or hairpin. Each arm of the hairpin can be processed into one member of a closely related family of short non-coding RNAs that are involved in regulating gene expression. The processed, or "mature" products of the precursor molecule are known as microRNA (miRNA), and have been predicted or confirmed in a wide range of speciessee 'MIPF0000009' in miRBase: the microRNA database. miRNA processing Animal miRNAs are first transcribed as a primary miRNA molecule. This "pri-miRNA" may contain one or more precursor hairpins, which are freed from the pri-miRNA by the nuclear enzyme Drosha. The approximately 70 nucleotide precursor hairpin is exported from the nucleus and subsequently processed by the Dicer enzyme to give a mature miRNA that is on average 22 nucleotides long. Either arm of the precursor may yield a mature RNA, although either the 3' (3p) or the 5' (5p) arm is preferentially proce ...
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AU-rich Element
Adenylate-uridylate-rich elements (AU-rich elements; AREs) are found in the 3' untranslated region (UTR) of many messenger RNAs (mRNAs) that code for proto-oncogenes, nuclear transcription factors, and cytokines. AREs are one of the most common determinants of RNA stability in mammalian cells. AREs are defined as a region with frequent adenine and uridine bases in a mRNA. They usually target the mRNA for rapid degradation. ARE-directed mRNA degradation is influenced by many exogenous factors, including phorbol esters, calcium ionophores, cytokines, and transcription inhibitors. These observations suggest that AREs play a critical role in the regulation of gene transcription during cell growth and differentiation, and the immune response. AREs have been divided into three classes with different sequences. The best characterised adenylate uridylate (AU)-rich Elements have a core sequence of AUUUA within U-rich sequences (for example WWWU(AUUUA)UUUW where W is A or U). This lies wi ...
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YWHAH
14-3-3 protein eta also referred to as 14-3-3η is a protein that in humans is encoded by the ''YWHAH'' gene. Function This gene product belongs to the 14-3-3 family of proteins that are normally intracellular in nature and help to mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat has been associated with early-onset schizophrenia. Protein-protein interactions YWHAH has been shown to interact with: * C-Raf, * CDC25B, * EPB41L3, * Glucocorticoid receptor, * KIF5B, * KLC3, * Phosphoinositide-dependent kinase-1, * RIMS1, * RIMS2, * TLX2, * TNFAIP3, and * ZFP36. Externalization 14-3-3n is normally intracellular. Two main mechanisms resulting in the release of 14-3-3η into the extracellular e ...
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ZFP36L1
Butyrate response factor 1 is a protein that in humans is encoded by the ''ZFP36L1'' gene. Function This gene is a member of the TIS11 family of early response genes. Family members are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. The gene is well conserved across species and has a promoter that contains motifs seen in other early-response genes. The encoded protein contains a distinguishing putative zinc finger domain with a repeating cys-his motif. This RNA binding protein most likely functions in regulating the response to growth factors. ZFP36L1 can degrade transcripts of numerous components of senescence-associated secretory phenotype (SASP) factors. Interactions ZFP36L1 has been shown to interact with MAPK14 Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the ''MAPK14'' gene. MAPK14 encodes p38α mitogen-activated protein kinase (MAPK) which is the prototypic member ...
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NUP214
Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the ''NUP214'' gene. Function The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene is a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is localized to the cytoplasmic face of the nuclear pore complex where it is required for proper cell cycle progression and nucleocytoplasmic transport. The 3' portion of this gene forms a fusion gene with the DEK gene on chromosome 6 in a t(6,9) translocation associated with acute myeloid leukemia and myelodysplastic syndrome. Structure The structure of the N-terminal domain of Nup214 reveals a sevenbladed beta-propeller fold followed by a 30-residue C-terminal extended peptide segment (CTE). The CTE folds back ...
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MicroRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then gene silence said mRNA molecules by one or more of the following processes: (1) cleavage of mRNA strand into two pieces, (2) destabilization of mRNA by shortening its poly(A) tail, or (3) translation of mRNA into proteins. This last method of gene silencing is the least efficient of the three, and requires the aid of ribosomes. miRNAs resemble the small interfering RNAs (siRNAs) of the RNA interference (RNAi) pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins, whereas siRNAs derive from longer regions of double-stranded RNA. The human genome may encode over 1900 miRNAs, although more recent analysis suggests that ...
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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 ...
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Subcellular Localization
The cells of eukaryotic organisms are elaborately subdivided into functionally-distinct membrane-bound compartments. Some major constituents of eukaryotic cells are: extracellular space, plasma membrane, cytoplasm, nucleus, mitochondria, Golgi apparatus, endoplasmic reticulum (ER), peroxisome, vacuoles, cytoskeleton, nucleoplasm, nucleolus, nuclear matrix and ribosomes. Bacteria also have subcellular localizations that can be separated when the cell is fractionated. The most common localizations referred to include the cytoplasm, the cytoplasmic membrane (also referred to as the inner membrane in Gram-negative bacteria), the cell wall (which is usually thicker in Gram-positive bacteria) and the extracellular environment. The cytoplasm, the cytoplasmic membrane and the cell wall are subcellular localizations, whereas the extracellular environment is clearly not. Most Gram-negative bacteria also contain an outer membrane and periplasmic space. Unlike eukaryotes, most bacteria cont ...
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Post-transcriptional Regulation
Post-transcriptional regulation is the control of gene expression at the RNA level. It occurs once the RNA polymerase has been attached to the gene's promoter and is synthesizing the nucleotide sequence. Therefore, as the name indicates, it occurs between the transcription phase and the translation phase of gene expression. These controls are critical for the regulation of many genes across human tissues. It also plays a big role in cell physiology, being implicated in pathologies such as cancer and neurodegenerative diseases. Mechanism After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA binding protein (RBP) that control the various steps and rates controlling events such as alternative splicing, nuclear degradation ( exosome), processing, nuclear export (three alternative pathways), sequestration in P-bodies for storage or degradation and ultimately translation. These proteins ac ...
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Nuclear Pore Complex
A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes (NPCs) in the nuclear envelope of a vertebrate cell, but this number varies depending on cell type and the stage in the life cycle. The human nuclear pore complex (hNPC) is a 110 megadalton (MDa) structure. The proteins that make up the nuclear pore complex are known as nucleoporins; each NPC contains at least 456 individual protein molecules and is composed of 34 distinct nucleoporin proteins. About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. The other half show structural characteristics typical of "natively unfolded" or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ord ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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