File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Protein arginine-methyltransferase-dependent oncogenesis

TitleProtein arginine-methyltransferase-dependent oncogenesis
Authors
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology
Citation
Nature Cell Biology, 2007, v. 9 n. 10, p. 1208-1215 How to Cite?
AbstractEnzymes that mediate reversible epigenetic modifications have not only been recognized as key in regulating gene expression and oncogenesis, but also provide potential targets for molecular therapy. Although the methylation of arginine 3 of histone 4 (H4R3) by protein arginine methyltransferase 1 (PRMT1) is a critical modification for active chromatin and prevention of heterochromatin spread, there has been no direct evidence of any role of PRMTs in cancer. Here, we show that PRMT1 is an essential component of a novel Mixed Lineage Leukaemia (MLL) oncogenic transcriptional complex with both histone acetylation and H4R3 methylation activities, which also correlate with the expression of critical MLL downstream targets. Direct fusion of MLL with PRMT1 or Sam68, a bridging molecule in the complex for PRMT1 interaction, could enhance self-renewal of primary haematopoietic cells. Conversely, specific knockdown of PRMT1 or Sam68 expression suppressed MLL-mediated transformation. This study not only functionally dissects the oncogenic transcriptional machinery associated with an MLL fusion complex, but also uncovers - for the first time - an essential function of PRMTs in oncogenesis and reveals their potential as novel therapeutic targets in human cancer.
Persistent Identifierhttp://hdl.handle.net/10722/148527
ISSN
2015 Impact Factor: 18.699
2015 SCImago Journal Rankings: 14.131
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheung, Nen_US
dc.contributor.authorChan, LCen_US
dc.contributor.authorThompson, Aen_US
dc.contributor.authorCleary, MLen_US
dc.contributor.authorSo, CWEen_US
dc.date.accessioned2012-05-29T06:13:31Z-
dc.date.available2012-05-29T06:13:31Z-
dc.date.issued2007en_US
dc.identifier.citationNature Cell Biology, 2007, v. 9 n. 10, p. 1208-1215en_US
dc.identifier.issn1465-7392en_US
dc.identifier.urihttp://hdl.handle.net/10722/148527-
dc.description.abstractEnzymes that mediate reversible epigenetic modifications have not only been recognized as key in regulating gene expression and oncogenesis, but also provide potential targets for molecular therapy. Although the methylation of arginine 3 of histone 4 (H4R3) by protein arginine methyltransferase 1 (PRMT1) is a critical modification for active chromatin and prevention of heterochromatin spread, there has been no direct evidence of any role of PRMTs in cancer. Here, we show that PRMT1 is an essential component of a novel Mixed Lineage Leukaemia (MLL) oncogenic transcriptional complex with both histone acetylation and H4R3 methylation activities, which also correlate with the expression of critical MLL downstream targets. Direct fusion of MLL with PRMT1 or Sam68, a bridging molecule in the complex for PRMT1 interaction, could enhance self-renewal of primary haematopoietic cells. Conversely, specific knockdown of PRMT1 or Sam68 expression suppressed MLL-mediated transformation. This study not only functionally dissects the oncogenic transcriptional machinery associated with an MLL fusion complex, but also uncovers - for the first time - an essential function of PRMTs in oncogenesis and reveals their potential as novel therapeutic targets in human cancer.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiologyen_US
dc.relation.ispartofNature Cell Biologyen_US
dc.subject.meshAcetylationen_US
dc.subject.meshAdaptor Proteins, Signal Transducing - Genetics - Metabolismen_US
dc.subject.meshArginine - Metabolismen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Transformation, Neoplastic - Genetics - Metabolismen_US
dc.subject.meshChromatin Immunoprecipitationen_US
dc.subject.meshDna-Binding Proteins - Genetics - Metabolismen_US
dc.subject.meshElectrophoresis, Polyacrylamide Gelen_US
dc.subject.meshFlow Cytometryen_US
dc.subject.meshFluorescent Antibody Techniqueen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHistones - Metabolismen_US
dc.subject.meshHomeodomain Proteins - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoprecipitationen_US
dc.subject.meshMethylationen_US
dc.subject.meshMutationen_US
dc.subject.meshPromoter Regions, Genetic - Geneticsen_US
dc.subject.meshProtein-Arginine N-Methyltransferases - Genetics - Metabolismen_US
dc.subject.meshRna-Binding Proteins - Genetics - Metabolismen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTransfectionen_US
dc.titleProtein arginine-methyltransferase-dependent oncogenesisen_US
dc.typeArticleen_US
dc.identifier.emailChan, LC:chanlc@hkucc.hku.hken_US
dc.identifier.authorityChan, LC=rp00373en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ncb1642en_US
dc.identifier.pmid17891136-
dc.identifier.scopuseid_2-s2.0-34848865728en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34848865728&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume9en_US
dc.identifier.issue10en_US
dc.identifier.spage1208en_US
dc.identifier.epage1215en_US
dc.identifier.eissn1476-4679-
dc.identifier.isiWOS:000249882300017-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.citeulike1720179-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats