rdf:type |
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lifeskim:mentions |
umls-concept:C0040715,
umls-concept:C0205314,
umls-concept:C0206694,
umls-concept:C0332466,
umls-concept:C0599718,
umls-concept:C0599813,
umls-concept:C0599893,
umls-concept:C0679622,
umls-concept:C1155452,
umls-concept:C1424876,
umls-concept:C1514468,
umls-concept:C1522702,
umls-concept:C1706214
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pubmed:issue |
2
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pubmed:dateCreated |
2003-1-31
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pubmed:databankReference |
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pubmed:abstractText |
Truncation of Notch1 has been shown to cause a subtype of acute leukemia, and activation of Notch4 has been associated with mammary and salivary gland carcinomas of mice. Here we identify a new mechanism for disrupting Notch signaling in human tumorigenesis, characterized by altered function of a new ortholog of the Drosophila melanogaster Notch co-activator molecule Mastermind. We cloned the t(11;19) translocation that underlies the most common type of human malignant salivary gland tumor. This rearrangement fuses exon 1 from a novel gene of unknown function at 19p13, termed mucoepidermoid carcinoma translocated 1 (MECT1), with exons 2-5 of a novel member of the Mastermind-like gene family (MAML2) at 11q21 (ref. 3). Similar to D. melanogaster Mastermind and MAML1 (refs. 4,5), full-length MAML2 functioned as a CSL (CBF-1, suppressor of hairless and Lag-1)-dependent transcriptional co-activator for ligand-stimulated Notch. In contrast, MECT1-MAML2 activated transcription of the Notch target gene HES1 independently of both Notch ligand and CSL binding sites. MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product. These data suggest a new mechanism to disrupt the function of a Notch co-activator in a common type of malignant salivary gland tumor.
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pubmed:commentsCorrections |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HES1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/JAG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MAML1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonuclease, Pancreatic,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/mastermind protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/notch protein, Drosophila
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:CoxonAmy BAB,
pubmed-author:El-NaggarAdelA,
pubmed-author:GriffinJames DJD,
pubmed-author:KayeFrederic JFJ,
pubmed-author:KirschIlan RIR,
pubmed-author:KomiyaTakefumiT,
pubmed-author:KuboAkihitoA,
pubmed-author:ModiSanjayS,
pubmed-author:O'NeilKevinK,
pubmed-author:StoverKristenK,
pubmed-author:TononGiovanniG,
pubmed-author:WuLiziL
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pubmed:issnType |
Print
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
208-13
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12539049-Animals,
pubmed-meshheading:12539049-Artificial Gene Fusion,
pubmed-meshheading:12539049-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:12539049-Carcinoma, Mucoepidermoid,
pubmed-meshheading:12539049-Carrier Proteins,
pubmed-meshheading:12539049-Chromosomes, Human, Pair 11,
pubmed-meshheading:12539049-Chromosomes, Human, Pair 19,
pubmed-meshheading:12539049-DNA-Binding Proteins,
pubmed-meshheading:12539049-Drosophila Proteins,
pubmed-meshheading:12539049-Drosophila melanogaster,
pubmed-meshheading:12539049-Gene Expression Regulation,
pubmed-meshheading:12539049-Gene Rearrangement,
pubmed-meshheading:12539049-Homeodomain Proteins,
pubmed-meshheading:12539049-Humans,
pubmed-meshheading:12539049-In Situ Hybridization, Fluorescence,
pubmed-meshheading:12539049-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12539049-Karyotyping,
pubmed-meshheading:12539049-Ligands,
pubmed-meshheading:12539049-Luciferases,
pubmed-meshheading:12539049-Membrane Proteins,
pubmed-meshheading:12539049-Molecular Sequence Data,
pubmed-meshheading:12539049-Mutation,
pubmed-meshheading:12539049-Neoplasms, Glandular and Epithelial,
pubmed-meshheading:12539049-Nuclear Proteins,
pubmed-meshheading:12539049-Promoter Regions, Genetic,
pubmed-meshheading:12539049-Receptors, Notch,
pubmed-meshheading:12539049-Repressor Proteins,
pubmed-meshheading:12539049-Ribonuclease, Pancreatic,
pubmed-meshheading:12539049-Salivary Gland Neoplasms,
pubmed-meshheading:12539049-Signal Transduction,
pubmed-meshheading:12539049-Trans-Activators,
pubmed-meshheading:12539049-Transcription, Genetic,
pubmed-meshheading:12539049-Transcription Factors,
pubmed-meshheading:12539049-Transcriptional Activation,
pubmed-meshheading:12539049-Transfection,
pubmed-meshheading:12539049-Translocation, Genetic,
pubmed-meshheading:12539049-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.
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pubmed:affiliation |
Genetics Branch, Center for Cancer Research, National Cancer Institute and the National Naval Medical Center, Bethesda, Maryland 20889, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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