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  • FLT3
  • Recently, treatment with bromodomain and extraterminal protein antagonist (BA) such as JQ1 has been shown to inhibit growth and induce apoptosis of human acute myelogenous leukemia (AML) cells, including those expressing FLT3-ITD. (aacrjournals.org)
  • Here, we demonstrate that cotreatment with JQ1 and the FLT3 tyrosine kinase inhibitor (TKI) ponatinib or AC220 synergistically induce apoptosis of cultured and primary CD34 + human AML blast progenitor cells (BPC) expressing FLT3-ITD. (aacrjournals.org)
  • Furthermore, cotreatment with JQ1 and the pan-histone deacetylase inhibitor (HDI) panobinostat synergistically induced apoptosis of FLT3-TKI-resistant MOLM13-TKIR and MV4-11-TKIR cells. (aacrjournals.org)
  • Several FLT3 kinase inhibitors (FLT3-TKI) have been clinically tested but none is yet approved for the therapy of AML ( 5, 6 ). (aacrjournals.org)
  • Recently, ponatinib was shown to be active against AC220-resistant kinase domain mutants of AML-expressing FLT3-ITD ( 6 , 11 ). (aacrjournals.org)
  • related kinases FLT3 and RET are also sensitive, with IC50=25 nM and IC50=17 nM, respectively. (wikipedia.org)
  • selective
  • Subsequent studies have confirmed that SU6656 is relatively selective for Src family kinases but some additional biochemical activities have been identified including: BRSK2, AMPK, Aurora C, Aurora B, CaMKKβ. (wikipedia.org)
  • In 2009 he was awarded the Lasker Clinical Award and in 2012 the Japan Prize for the development of Gleevec, a selective BCR-ABL inhibitor for the treatment of chronic myeloid leukaemia (CML), which converted a fatal cancer into a manageable chronic condition. (wikipedia.org)
  • TKIs
  • Numerous TKIs aiming at various tyrosine kinases have been generated by the originators of these compounds and proven to be effective anti-tumor agents and anti-leukemic agents. (wikipedia.org)
  • Recently TKIs have been shown to deprive tyrosine kinases of access to the Cdc37-Hsp90 molecular chaperone system on which they depend for their cellular stability, leading to their ubiquitylation and degradation. (wikipedia.org)
  • residues
  • The results supported the proposed function of the enzyme, as the amount of abnormal L-aspartate residues increased when cells were treated with the indirect inhibitor, adenosine dialdehyde. (wikipedia.org)
  • When PIMT is not present in cells, the abnormal aspartyl residues accumulate, creating abnormal proteins that have been known to cause fatal progressive epilepsy in mice. (wikipedia.org)
  • encode
  • However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers. (wikipedia.org)
  • These fusion genes encode fusion proteins that continuously stimulate cell growth, proliferation, prolonged survival, and/or differentiation. (wikipedia.org)
  • Therapeutics
  • Accordingly, our data provide valuable information for the further development of therapeutics targeting Lyn and the important Src-family of kinases. (edu.au)
  • peptide
  • Additional structures (3G60 and 3G61) of P-gp were also solved revealing the binding site(s) of two different cyclic peptide substrate/inhibitors. (wikipedia.org)
  • activity
  • We report here that Shigella invasion of epithelial cells requires rho activity, a ras-related GTP-binding protein. (rupress.org)
  • Although several Src-family inhibitors are available, the development of Lyn-specific inhibitors, or inhibitors with reduced off-target activity to Lyn, has been hampered by the lack of structural data on the Lyn kinase. (edu.au)
  • One such inhibitor, the p.o. active ZD1839 (Iressa), has pronounced antiproliferative activity against human tumor xenografts. (aacrjournals.org)
  • A 2015 review of polymorphisms in ABCB1 found that "the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. (wikipedia.org)
  • With the discovery of the uncontrolled tyrosine kinase activity of this disorder and the use of tyrosine kinase inhibitors. (wikipedia.org)
  • sensitivity
  • Based on their association with eosinophils, unique genetic mutations, and known or potential sensitivity to tyrosine kinase inhibitors or other specific drug therapies, they are now in the process of being classified together under the term clonal hypereosinophilia or clonal eosinophilia. (wikipedia.org)
  • stimulate
  • The mutations cause these proteins to be continuously active and thereby to stimulate growth in an uncontrolled and continuous manner. (wikipedia.org)
  • cells
  • Effects of protein tyrosine kinase inhibitors on cytokine-induced adhesion molecule expression by human umbilical vein endothelial cells. (mysciencework.com)
  • Cells were harvested 18 h after transfection and lysed at 4 C in a Dounce homogenizer in 250 mm sucrose, 20 mm TrisHCl, 1 mm CaCl2, 1 mm MgCl2, cOmplete protease inhibitor cocktail (Roche Applied Science), pH 8. (molecularcircuit.com)
  • P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. (wikipedia.org)
  • As these proteins accumulate, they begin to form plaques that interfere with signaling between cells of the nervous system found within the brain. (wikipedia.org)
  • In treated cells the inhibitor blocks downstream cellular signalling (JAK-STAT) leading to suppression of proliferation and induction of apoptosis. (wikipedia.org)
  • dialdehyde
  • Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. (hindawi.com)
  • regulates
  • The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. (wikipedia.org)
  • Initially
  • SU6656 was initially identified as a Src kinase inhibitor by virtue of its ability to reverse an effect that an activated mutant form of Src (hu SRC Y530F) has on the actin cytoskeleton, namely the formation of podosome rosettes, otherwise known as invadopodia. (wikipedia.org)
  • known
  • ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ETV6 (previously known as TEL) gene. (wikipedia.org)
  • substrates
  • This protein functions as a multispecific organic anion transporter, with oxidized glutathione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. (wikipedia.org)
  • accumulation
  • One of the more prominent signs of Alzheimer's disease is the accumulation of β-amyloid proteins in the brain. (wikipedia.org)
  • The transporter protein has been shown to decrease β-amyloid accumulation by nearly 80 percent when activated, leading researchers to further investigation on its use in future treatments of Alzheimer's and other neurological disorders. (wikipedia.org)
  • small molecule inhibitor
  • Years later, a small molecule inhibitor of the VEGFR2 kinase function was developed, from which a derivative was approved in 2006 for the treatment of kidney carcinoma and gastro-intestinal stromal tumors. (wikipedia.org)
  • Tasquinimod is a novel small-molecule inhibitor that targets the tumor microenvironment by controlling the accumulation and immunosuppressive, pro-angiogenic and pro-metastatic functions of regulatory myeloid cells (also called myeloid-derived suppressor cells). (wikipedia.org)
  • induces
  • This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)
  • TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a consequence, act to halt the cell cycle and stop proliferation. (wikipedia.org)
  • oncogene
  • Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL) located on chromosome 9. (wikipedia.org)
  • Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. (wikipedia.org)
  • His track record includes the discovery of the N-Ras oncogene , the identification of farnesylation of Ras proteins, and the discovery that Ras signals through the MAPK/ERK pathway. (wikipedia.org)
  • ligand
  • J Am Chem Soc 127:4625-4631 Martin E, Berka V, Bogatenkova E, Murad F, Tsai A L (2006) Ligand selectivity of soluble guanylyl cyclase - effect of the hydrogen-bonding tyrosine in the distal heme pocket on binding of oxygen, nitric oxide, and carbon monoxide. (alusdomundo.com)
  • interacts
  • this MKB/KIM motif of DUSP interacts with the common domain of MAP kinases to mediate the enzyme-substrate interaction [ 1 ]. (scitechnol.com)
  • When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the flexible linker domain and thereby keeps the inactive unit tightly bound. (wikipedia.org)
  • binds
  • An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. (wikipedia.org)
  • A well-characterised example of this is the ribonuclease inhibitor, which binds to ribonucleases in one of the tightest known protein-protein interactions. (wikipedia.org)
  • CPSF1 is an RNA processing protein that binds to uracil-rich sequences in pre-mRNA, concurrently binds with and stimulates POPOLA, i.e. (wikipedia.org)
  • alterations
  • Ullrich is also Principal Investigator of Singapore Oncogenome Project at the Institute of Medical Biology aimed at identifying all oncogenic alterations in all protein tyrosine kinase (PTK) gene transcripts of a large number of tumor cell lines and primary tumors. (wikipedia.org)
  • enzyme
  • c-Src stands for "cellular Src kinase" and should not be confused with "C-terminal Src kinase" (CSK) which is an enzyme which phosphorylates c-Src at its C-terminus and provides negative regulation of Src's enzymatic activity. (wikipedia.org)
  • In response to interferon, cells produce large amounts of an enzyme known as protein kinase R (PKR). (wikipedia.org)
  • Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. (wikipedia.org)
  • The binding of an inhibitor can stop a substrate from entering the enzyme's active site and/or hinder the enzyme from catalyzing its reaction. (wikipedia.org)
  • Many drug molecules are enzyme inhibitors, so their discovery and improvement is an active area of research in biochemistry and pharmacology. (wikipedia.org)
  • Enzyme inhibitors also occur naturally and are involved in the regulation of metabolism. (wikipedia.org)
  • Natural enzyme inhibitors can also be poisons and are used as defences against predators or as ways of killing prey. (wikipedia.org)
  • There are four kinds of reversible enzyme inhibitors. (wikipedia.org)
  • PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene. (wikipedia.org)
  • Thus, in evolution, the FYVE-domain-containing phosphoinositide kinases retain several aspects of the structural organization, enzyme activity and protein interactions from budding yeast. (wikipedia.org)
  • adhesion
  • Vascular endothelial cadherin (VE-cadherin), an endothelium-specific member of the cadherin family members of adhesion protein (Bach et al . (code3systems.com)
  • viral
  • Activator protein 1 (AP-1) is a transcription factor that regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. (wikipedia.org)
  • A 1989 in vitro study found that piceatannol blocked LMP2A, a viral protein-tyrosine kinase implicated in leukemia, non-Hodgkin's lymphoma and other diseases associated with Epstein-Barr virus. (wikipedia.org)
  • localize
  • In both invertebrates and mammals, Numb is localized using the Pins/GαI complex and the PAR complex of Bazooka (Par3 in mammals), Par6, and aPKC (atypical protein kinase C). In the sensory organ precursor (SOP) cell, the PAR proteins localize to the posterior pole of the cell, and the Pins/GαI complex is localized to the anterior pole of the cell. (wikipedia.org)
  • Additional data in support of this theory was later obtained from studies in zebrafish, where its Cdc14 proteins were also found to localize to the basal body and play roles in the formation of cilia, which are short forms of flagella. (wikipedia.org)
  • angiogenesis
  • 1998 ), and various other Camera protein, such as PECAM-1, ICAM-1, and Alogliptin IC50 JAM-A, are also connected to angiogenesis Alogliptin IC50 (Bach et al . (code3systems.com)
  • Even more significantly, IGPR-1 colleagues with many SH3-formulated with protein and adjusts angiogenesis in vivo and in vitro. (code3systems.com)
  • mammalian
  • PtdIns5P, made by PIKfyve kinase activity in mammalian cells, is not detected in budding yeast. (wikipedia.org)
  • The yeast Fab1 complex also includes Vac7p and probably Atg18p, proteins that are not detected in the mammalian PIKfyve complex. (wikipedia.org)
  • embryonic development
  • In contrast, the knockout of the FYVE domain-containing enzymes in A. thaliana, D. melanogaster, C. elegans and M. musculus leads to embryonic lethality indicating that the FYVE-domain-containing phosphoinositide kinases have become essential in embryonic development of multicellular organisms. (wikipedia.org)
  • In higher eukaryotes, the enzymes acquire one additional domain, a role in the production of PtdIns5P, a new set of interacting proteins and become essential in embryonic development. (wikipedia.org)
  • Domain
  • In support of this hypothesis, an H-NOX domain and a predicted histidine kinase from Shewanella oneidensis were isolated and found to interact in vitro. (alusdomundo.com)
  • c-Src includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. (wikipedia.org)
  • By directly binding membrane PtdIns(3)P, the FYVE finger domain of PIKfyve is essential in localizing the protein to the cytosolic leaflet of endosomes. (wikipedia.org)
  • MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the MECOM gene. (wikipedia.org)
  • The MECOM protein contains 2 domains characterized by 7 zinc finger motifs followed by a proline-rich transcription repression domain, 3 more zinc finger motifs and an acidic C-terminus. (wikipedia.org)
  • mediate
  • Src contains at least three flexible protein domains, which, in conjunction with myristoylation, can mediate attachment to membranes and determine subcellular localization. (wikipedia.org)
  • functional
  • Additionally, the functional interaction between the H-NOX and kinase was mediated by NO (Price et al. (alusdomundo.com)
  • PIKfyve is a large protein, containing a number of functional domains and expressed in several spliced forms. (wikipedia.org)
  • cell
  • Genetic combinatorial marking using lentiviral vectors encoding fluorescent proteins (FPs) enabled cell fate mapping through advanced microscopy imaging. (jove.com)
  • His work in the field of cell signalling showed how RAS and other signalling proteins are involved in transmitting signals from outside of the cell all the way to the cell nucleus. (wikipedia.org)
  • The numb gene protein product controls binary cell fate decisions in the peripheral and central nervous systems of both invertebrates and mammals during neurogenesis. (wikipedia.org)
  • Numb protein signaling plays a key role in binary cell fate decisions following asymmetric cell divisions. (wikipedia.org)
  • Numb's primary function in cell differentiation is as an inhibitor of Notch signaling which is essential for maintaining self-renewal potential in stem and progenitor cells. (wikipedia.org)
  • Consistent with such multiple roles, ScCdc14 has been found to bind several proteins that regulate the cell cycle and DNA replication, or that associate with the spindle or kinetochore. (wikipedia.org)
  • family
  • TGF-β, along with other TGF-β family ligands such as bone morphogenic protein (BMP) and activin are involved in regulating important cellular functions such as proliferation, differentiation, apoptosis, and matrix production. (wikipedia.org)
  • molecules
  • IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. (wikipedia.org)
  • The BCR-ABL protein can be inhibited by various small molecules. (wikipedia.org)
  • tumor
  • Interferons (IFNs) are a group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. (wikipedia.org)
  • regulation
  • Thus, the activation of the HBP by nutrients represents a biochemical link between nutrient availability, mitochondrial proteins, and energy expenditure, and it is likely to play an important role in the regulation of energy balance. (jci.org)
  • promoter
  • We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. (jci.org)
  • When expressing the Tet-On 3G transactivator protein from the EF-1 alpha promoter, 83% of the Jurkat Tet-On 3G clones showed strong inducible expression and 33% demonstrated very high inducibility (greater than 2,000-fold). (clontech.com)
  • activation
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)
  • Apart from the "leucine zipper" and the "basic region" which are important for dimerization and DNA-binding, the c-jun protein contains three short regions, which consist of clusters of negatively charged amino acids in its N-terminal half that are important for transcriptional activation in vivo. (wikipedia.org)
  • humans
  • also termed Pre-mRNA 3'-end-processing factor FIP1) is a protein that in humans is encoded by the FIP1L1 gene (also known as Rhe, FIP1, and hFip1). (wikipedia.org)
  • processes
  • Many early studies, especially in the budding yeast Saccharomyces cerevisiae, demonstrated that the protein plays a key role in regulating late mitotic processes. (wikipedia.org)