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Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation

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dc.contributor.author Georges R.
dc.contributor.author Nemer G.
dc.contributor.author Morin M.
dc.contributor.author Lefebvre C.
dc.contributor.author Nemer M.
dc.contributor.editor
dc.date Jun-2008
dc.date.accessioned 2017-10-05T15:30:54Z
dc.date.available 2017-10-05T15:30:54Z
dc.date.issued 2008
dc.identifier 10.1128/MCB.02100-07
dc.identifier.isbn
dc.identifier.issn 02707306
dc.identifier.uri http://hdl.handle.net/10938/15273
dc.description.abstract Mutations in the T-box transcription factor Tbx5 cause Holt-Oram syndrome, an autosomal dominant disease characterized by a wide spectrum of cardiac and upper limb defects with variable expressivity. Tbx5 haploinsufficiency has been suggested to be the underlying mechanism, and experimental models are consistent with a dosage-sensitive requirement for Tbx5 in heart development. Here, we report that Tbx5 levels are regulated through alternative splicing that generates, in addition to the known 518-amino-acid protein, a C-terminal truncated isoform. This shorter isoform retains the capacity to bind DNA, but its interaction with Tbx5 collaborators such as GATA-4 is altered. In vivo, the two spliced isoforms are oppositely regulated in a temporal and growth factor-dependent manner and are present in distinct DNA-binding complexes. The expression of the long isoform correlates with growth stimulation, and its reexpression in postnatal transgenic mouse hearts promotes hypertrophy. Conversely, the upregulation of the short but not the long isoform in C2C12 myoblasts leads to growth arrest and cell death. The results provide novel insight into posttranscriptional Tbx5 regulation and point to an important role not only in cell differentiation but also in cell proliferation and organ growth. The data may help analyze genotype-phenotype relations in patients with Holt-Oram syndrome. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
dc.format.extent
dc.format.extent Pages: (4052-4057)
dc.language English
dc.relation.ispartof Publication Name: Molecular and Cellular Biology; Publication Year: 2008; Volume: 28; no. 12; Pages: (4052-4057);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation
dc.type Article
dc.contributor.affiliation Georges, R., Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada, Programme de Biologie Moléculaire, Université de Montréal, Montréal, QC, Canada
dc.contributor.affiliation Nemer, G., Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada, Programme de Biologie Moléculaire, Université de Montréal, Montréal, QC, Canada, Department of Biochemistry, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Morin, M., Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada, Programme de Biologie Moléculaire, Université de Montréal, Montréal, QC, Canada
dc.contributor.affiliation Lefebvre, C., Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada
dc.contributor.affiliation Nemer, M., Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada, Programme de Biologie Moléculaire, Université de Montréal, Montréal, QC, Canada, Department of Biochemistry, University of Ottawa, Ottawa, ON, Canada, Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada
dc.contributor.authorAddress Nemer, M.; Research Unit in Cardiac Growth and Differentiation, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada; email: mona.nemer@ircm.qc.ca
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Biochemistry and Molecular Genetics;
dc.contributor.authorDepartment Biochemistry and Molecular Genetics
dc.contributor.authorDivision
dc.contributor.authorEmail
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
dc.description.cited
dc.description.citedCount 19
dc.description.citedTotWOSCount
dc.description.citedWOSCount
dc.format.extentCount 6
dc.identifier.articleNo
dc.identifier.coden MCEBD
dc.identifier.pubmedID 18391012
dc.identifier.scopusID 44949133142
dc.identifier.url
dc.publisher.address
dc.relation.ispartofConference
dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr
dc.relation.ispartOfIssue 12
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Molecular and Cellular Biology
dc.relation.ispartofPubTitleAbbr Mol. Cell. Biol.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 28
dc.source.ID
dc.type.publication Journal
dc.subject.otherAuthKeyword
dc.subject.otherChemCAS Gata4 protein, mouse
dc.subject.otherChemCAS GATA4 Transcription Factor
dc.subject.otherChemCAS Protein Isoforms
dc.subject.otherChemCAS T-Box Domain Proteins
dc.subject.otherChemCAS T-box transcription factor 5
dc.subject.otherIndex transcription factor TBX5
dc.subject.otherIndex animal cell
dc.subject.otherIndex article
dc.subject.otherIndex carboxy terminal sequence
dc.subject.otherIndex cell death
dc.subject.otherIndex cell differentiation
dc.subject.otherIndex cell growth
dc.subject.otherIndex cell proliferation
dc.subject.otherIndex DNA binding
dc.subject.otherIndex growth stimulation
dc.subject.otherIndex hypertrophy
dc.subject.otherIndex in vivo study
dc.subject.otherIndex mouse
dc.subject.otherIndex myoblast
dc.subject.otherIndex nonhuman
dc.subject.otherIndex organ growth
dc.subject.otherIndex priority journal
dc.subject.otherIndex transgenic mouse
dc.subject.otherIndex upregulation
dc.subject.otherIndex Alternative Splicing
dc.subject.otherIndex Animals
dc.subject.otherIndex Cell Differentiation
dc.subject.otherIndex Cell Proliferation
dc.subject.otherIndex GATA4 Transcription Factor
dc.subject.otherIndex Gene Expression Regulation
dc.subject.otherIndex Genotype
dc.subject.otherIndex Mice
dc.subject.otherIndex Mice, Transgenic
dc.subject.otherIndex Models, Biological
dc.subject.otherIndex NIH 3T3 Cells
dc.subject.otherIndex Phenotype
dc.subject.otherIndex Protein Isoforms
dc.subject.otherIndex Reverse Transcriptase Polymerase Chain Reaction
dc.subject.otherIndex T-Box Domain Proteins
dc.subject.otherIndex Mus musculus
dc.subject.otherKeywordPlus
dc.subject.otherWOS


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