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  • 1
    Publication Date: 2014-06-12
    Description: Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR) defend against pathogen infection by activating caspase 1. Pyrin, a candidate PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating complex. Mutations in the Pyrin-encoding gene, MEFV, cause a human autoinflammatory disease known as familial Mediterranean fever. Despite important roles in immunity and disease, the physiological function of Pyrin remains unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in response to Rho-glucosylation activity of cytotoxin TcdB, a major virulence factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea. The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating activity. Other Rho-inactivating toxins, including FIC-domain adenylyltransferases (Vibrio parahaemolyticus VopS and Histophilus somni IbpA) and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically activate the Pyrin inflammasome in their enzymatic activity-dependent manner. These toxins all target the Rho subfamily and modify a switch-I residue. We further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome activation, both of which require the bacterial type VI secretion system (T6SS). Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B. cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to sense pathogen modification and inactivation of Rho GTPases, representing a new paradigm in mammalian innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Hao -- Yang, Jieling -- Gao, Wenqing -- Li, Lin -- Li, Peng -- Zhang, Li -- Gong, Yi-Nan -- Peng, Xiaolan -- Xi, Jianzhong Jeff -- Chen, She -- Wang, Fengchao -- Shao, Feng -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Sep 11;513(7517):237-41. doi: 10.1038/nature13449. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] National Institute of Biological Sciences, Beijing 102206, China [2]. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [3]. ; National Institute of Biological Sciences, Beijing 102206, China. ; Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [3] National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacterial Toxins/genetics/metabolism ; Burkholderia cenocepacia/metabolism ; Caspase 1/metabolism ; Cell Line ; Clostridium difficile/metabolism ; Cytoskeletal Proteins/genetics/*metabolism ; Humans ; Immunity, Innate/genetics/*immunology ; Inflammasomes/*metabolism ; Mice ; Mice, Inbred Strains ; Mutation ; Protein Binding ; Receptors, Pattern Recognition/metabolism ; U937 Cells ; rho GTP-Binding Proteins/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-07-24
    Description: Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, specifically PI(3)Kgamma. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754787/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Pulin -- Lahvic, Jamie L -- Binder, Vera -- Pugach, Emily K -- Riley, Elizabeth B -- Tamplin, Owen J -- Panigrahy, Dipak -- Bowman, Teresa V -- Barrett, Francesca G -- Heffner, Garrett C -- McKinney-Freeman, Shannon -- Schlaeger, Thorsten M -- Daley, George Q -- Zeldin, Darryl C -- Zon, Leonard I -- 1R01HL097794-04/HL/NHLBI NIH HHS/ -- 5P30 DK49216/DK/NIDDK NIH HHS/ -- 5R01DK53298/DK/NIDDK NIH HHS/ -- 5U01 HL10001-05/HL/NHLBI NIH HHS/ -- P015P01HL32262-32/HL/NHLBI NIH HHS/ -- P30-HD18655/HD/NICHD NIH HHS/ -- P50-NS40828/NS/NINDS NIH HHS/ -- R01 CA148633/CA/NCI NIH HHS/ -- R01 HL04880/HL/NHLBI NIH HHS/ -- R0CA148633-01A5/PHS HHS/ -- R24 DK092760/DK/NIDDK NIH HHS/ -- Z01 ES025034/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Jul 23;523(7561):468-71. doi: 10.1038/nature14569.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Stem Cell Program and Division of Haematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachuestts 02115, USA [2] Chemical Biology Program, Harvard University, Cambridge, Massachusetts 02138, USA. ; Stem Cell Program and Division of Haematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachuestts 02115, USA. ; 1] Stem Cell Program and Division of Haematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachuestts 02115, USA [2] Department of Hematology and Oncology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, 80337 Munich, Germany. ; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Haematology, St Jude Children's Research Hospital, Memphis, Tennessee 38105-3678, USA. ; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26201599" target="_blank"〉PubMed〈/a〉
    Keywords: 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/metabolism ; Animals ; Cell Line ; Cell Movement ; Core Binding Factor Alpha 2 Subunit/metabolism ; Female ; Gene Expression Regulation ; *Hematopoiesis ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney/cytology ; Male ; Mice ; Phosphatidylinositol 3-Kinases ; Transcription Factor AP-1/metabolism ; Transcription, Genetic ; Zebrafish/*embryology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2010-10-19
    Description: The derivation of human ES cells (hESCs) from human blastocysts represents one of the milestones in stem cell biology. The full potential of hESCs in research and clinical applications requires a detailed understanding of the genetic network that governs the unique properties of hESCs. Here, we report a genome-wide RNA interference screen to identify genes which regulate self-renewal and pluripotency properties in hESCs. Interestingly, functionally distinct complexes involved in transcriptional regulation and chromatin remodelling are among the factors identified in the screen. To understand the roles of these potential regulators of hESCs, we studied transcription factor PRDM14 to gain new insights into its functional roles in the regulation of pluripotency. We showed that PRDM14 regulates directly the expression of key pluripotency gene POU5F1 through its proximal enhancer. Genome-wide location profiling experiments revealed that PRDM14 colocalized extensively with other key transcription factors such as OCT4, NANOG and SOX2, indicating that PRDM14 is integrated into the core transcriptional regulatory network. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Altogether, our study uncovers a wealth of novel hESC regulators wherein PRDM14 exemplifies a key transcription factor required for the maintenance of hESC identity and the reacquisition of pluripotency in human somatic cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chia, Na-Yu -- Chan, Yun-Shen -- Feng, Bo -- Lu, Xinyi -- Orlov, Yuriy L -- Moreau, Dimitri -- Kumar, Pankaj -- Yang, Lin -- Jiang, Jianming -- Lau, Mei-Sheng -- Huss, Mikael -- Soh, Boon-Seng -- Kraus, Petra -- Li, Pin -- Lufkin, Thomas -- Lim, Bing -- Clarke, Neil D -- Bard, Frederic -- Ng, Huck-Hui -- England -- Nature. 2010 Nov 11;468(7321):316-20. doi: 10.1038/nature09531. Epub 2010 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20953172" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Cellular Reprogramming/genetics ; DNA-Binding Proteins/genetics/metabolism ; Embryonic Stem Cells/*cytology/*metabolism ; Enhancer Elements, Genetic/genetics ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation/genetics ; Genome, Human/*genetics ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Mice ; Octamer Transcription Factor-3/genetics/metabolism ; *RNA Interference ; Repressor Proteins/genetics/*metabolism ; SOXB1 Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1995-09-29
    Description: The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1 beta converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bump, N J -- Hackett, M -- Hugunin, M -- Seshagiri, S -- Brady, K -- Chen, P -- Ferenz, C -- Franklin, S -- Ghayur, T -- Li, P -- AI 38262/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 29;269(5232):1885-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BASF Bioresearch Corporation, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569933" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Apoptosis ; Binding Sites ; Binding, Competitive ; Caspase 1 ; Cell Line ; Cysteine Endopeptidases/*metabolism ; Cysteine Proteinase Inhibitors/genetics/*metabolism/pharmacology ; Enzyme Activation/drug effects ; Humans ; Inhibitor of Apoptosis Proteins ; Molecular Sequence Data ; Recombinant Proteins/pharmacology ; Transfection ; Viral Proteins/genetics/*metabolism/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2003-04-12
    Description: Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. The development of these abnormalities was reduced by treatment with Gleevec, an inhibitor of PDGF signaling. Thus, LRP1 has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling PDGFR activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucher, Philippe -- Gotthardt, Michael -- Li, Wei-Ping -- Anderson, Richard G W -- Herz, Joachim -- GM 52016/GM/NIGMS NIH HHS/ -- HL20948/HL/NHLBI NIH HHS/ -- HL63762/HL/NHLBI NIH HHS/ -- NS43408/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):329-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690199" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta/cytology/metabolism/*pathology ; Arteriosclerosis/*pathology/physiopathology/*prevention & control ; Benzamides ; Cattle ; Cell Division ; Cell Line ; Cholesterol, Dietary/administration & dosage ; Diet, Atherogenic ; Elastin/analysis ; Enzyme Inhibitors/pharmacology ; Imatinib Mesylate ; Ligands ; Low Density Lipoprotein Receptor-Related ; Protein-1/genetics/metabolism/*physiology ; Mesenteric Arteries/cytology/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Muscle, Smooth, Vascular/cytology/*metabolism/pathology ; Myocytes, Smooth Muscle/*metabolism/physiology ; Phosphorylation ; Piperazines/pharmacology ; Platelet-Derived Growth Factor/metabolism/pharmacology ; Proto-Oncogene Proteins c-sis ; Pyrimidines/pharmacology ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2003-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woods, Gordon L -- White, Kenneth L -- Vanderwall, Dirk K -- Li, Guang-Peng -- Aston, Kenneth I -- Bunch, Thomas D -- Meerdo, Lora N -- Pate, Barry J -- New York, N.Y. -- Science. 2003 Aug 22;301(5636):1063. Epub 2003 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Northwest Equine Reproduction Laboratory, Department of Animal and Veterinary Science, University of Idaho, Moscow, ID 83844, USA. gwoods@uidaho.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12775846" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cell Line ; *Cloning, Organism ; Embryo Transfer ; Embryo, Mammalian ; Embryonic and Fetal Development ; Equidae/*embryology/*genetics ; Female ; Fibroblasts ; Horses ; Male ; *Nuclear Transfer Techniques ; Oocytes/metabolism ; Pregnancy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2008-02-16
    Description: The majority of mitochondrial DNA (mtDNA) mutations that cause human disease are mild to moderately deleterious, yet many random mtDNA mutations would be expected to be severe. To determine the fate of the more severe mtDNA mutations, we introduced mtDNAs containing two mutations that affect oxidative phosphorylation into the female mouse germ line. The severe ND6 mutation was selectively eliminated during oogenesis within four generations, whereas the milder COI mutation was retained throughout multiple generations even though the offspring consistently developed mitochondrial myopathy and cardiomyopathy. Thus, severe mtDNA mutations appear to be selectively eliminated from the female germ line, thereby minimizing their impact on population fitness.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049809/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fan, Weiwei -- Waymire, Katrina G -- Narula, Navneet -- Li, Peng -- Rocher, Christophe -- Coskun, Pinar E -- Vannan, Mani A -- Narula, Jagat -- Macgregor, Grant R -- Wallace, Douglas C -- AG13154/AG/NIA NIH HHS/ -- AG16573/AG/NIA NIH HHS/ -- AG24373/AG/NIA NIH HHS/ -- DK73691/DK/NIDDK NIH HHS/ -- HD45913/HD/NICHD NIH HHS/ -- NS21328/NS/NINDS NIH HHS/ -- U01 HD045913-01/HD/NICHD NIH HHS/ -- U01 HD045913-02/HD/NICHD NIH HHS/ -- U01 HD045913-03/HD/NICHD NIH HHS/ -- U01 HD045913-04/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2008 Feb 15;319(5865):958-62. doi: 10.1126/science.1147786.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276892" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiomyopathies/genetics/pathology ; Cell Line ; Crosses, Genetic ; DNA, Mitochondrial/*genetics ; Electron Transport Complex I/metabolism ; Electron Transport Complex IV/*genetics/metabolism ; Embryonic Stem Cells ; Female ; Frameshift Mutation ; *Germ-Line Mutation ; Litter Size ; Male ; Mice ; Mitochondria/physiology ; Mitochondrial Myopathies/*genetics/pathology ; Mutation, Missense ; Myocardium/pathology ; NADH Dehydrogenase/*genetics ; Oocytes/*physiology ; Oogenesis ; Oxidative Phosphorylation ; Oxygen Consumption ; Point Mutation ; *Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2010-09-03
    Description: Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer's disease. Formation of amyloid-beta is catalysed by gamma-secretase, a protease with numerous substrates. Little is known about the molecular mechanisms that confer substrate specificity on this potentially promiscuous enzyme. Knowledge of the mechanisms underlying its selectivity is critical for the development of clinically effective gamma-secretase inhibitors that can reduce amyloid-beta formation without impairing cleavage of other gamma-secretase substrates, especially Notch, which is essential for normal biological functions. Here we report the discovery of a novel gamma-secretase activating protein (GSAP) that drastically and selectively increases amyloid-beta production through a mechanism involving its interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment (APP-CTF). GSAP does not interact with Notch, nor does it affect its cleavage. Recombinant GSAP stimulates amyloid-beta production in vitro. Reducing GSAP concentrations in cell lines decreases amyloid-beta concentrations. Knockdown of GSAP in a mouse model of Alzheimer's disease reduces levels of amyloid-beta and plaque development. GSAP represents a type of gamma-secretase regulator that directs enzyme specificity by interacting with a specific substrate. We demonstrate that imatinib, an anticancer drug previously found to inhibit amyloid-beta formation without affecting Notch cleavage, achieves its amyloid-beta-lowering effect by preventing GSAP interaction with the gamma-secretase substrate, APP-CTF. Thus, GSAP can serve as an amyloid-beta-lowering therapeutic target without affecting other key functions of gamma-secretase.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936959/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936959/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Gen -- Luo, Wenjie -- Li, Peng -- Remmers, Christine -- Netzer, William J -- Hendrick, Joseph -- Bettayeb, Karima -- Flajolet, Marc -- Gorelick, Fred -- Wennogle, Lawrence P -- Greengard, Paul -- AG09464/AG/NIA NIH HHS/ -- P01 AG009464/AG/NIA NIH HHS/ -- P01 AG009464-16A10010/AG/NIA NIH HHS/ -- T32 DK007017/DK/NIDDK NIH HHS/ -- England -- Nature. 2010 Sep 2;467(7311):95-8. doi: 10.1038/nature09325.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20811458" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*metabolism ; Amyloid Precursor Protein Secretases/chemistry/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/chemistry/metabolism ; Animals ; Benzamides ; Cell Line ; Disease Models, Animal ; Gene Knockdown Techniques ; Humans ; Imatinib Mesylate ; Mice ; Peptide Fragments/metabolism ; Piperazines/pharmacology ; Proteins/*antagonists & inhibitors/genetics/*metabolism ; Pyrimidines/pharmacology ; RNA Interference ; Receptor, Notch1/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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