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Article: Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes

TitleDominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes
Authors
Issue Date2004
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2004, v. 101 n. 1, p. 43-47 How to Cite?
AbstractHormonal induction of growth-arrested 3T3-L1 preadipocytes rapidly activates expression of CCAAT/enhancer-binding protein (C/EBP) β. Acquisition of DNA-binding activity by C/EBPβ, however, is delayed until the cells synchronously enter the S phase of mitotic clonal expansion (MCE). After MCE, C/EBPβ activates expression of C/EBPα and peroxisome proliferator-activated receptor γ, which then transcriptionally activate genes that give rise to the adipocyte phenotype. A-C/EBP, which possesses a leucine zipper but lacks functional DNA-binding and transactivation domains, forms stable inactive heterodimers with C/EBPβ in vitro. Infection of 3T3-L1 preadipocytes with an adenovirus A-C/EBP expression vector interferes with C/EBPβ function after induction of differentiation. A-C/EBP inhibited events associated with hormone-induced entry of S-phase of the cell cycle, including the turnover of p27/Kip1, a key cyclin-dependent kinase inhibitor, expression of cyclin A and cyclin-dependent kinase 2, DNA replication, MCE, and, subsequently, adipogenesis. Although A-C/EBP blocked cell proliferation associated with MCE, it did not inhibit normal proliferation of 3T3-L1 preadipocytes. Immunofluorescent staining of C/EBPβ revealed that A-C/EBP prevented the normal punctate nuclear staining of centromeres, an indicator of C/EBPβ binding to C/EBP regulatory elements in centromeric satellite DNA. The inhibitory effects of A-C/EBP appear to be due primarily to interference with nuclear import of C/EBPβ caused by obscuring its nuclear localization signal. These findings show that both MCE and adipogenesis are dependent on C/EBPβ.
Persistent Identifierhttp://hdl.handle.net/10722/180721
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, JWen_US
dc.contributor.authorTang, QQen_US
dc.contributor.authorVinson, Cen_US
dc.contributor.authorLane, MDen_US
dc.date.accessioned2013-01-28T01:41:58Z-
dc.date.available2013-01-28T01:41:58Z-
dc.date.issued2004en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2004, v. 101 n. 1, p. 43-47en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/180721-
dc.description.abstractHormonal induction of growth-arrested 3T3-L1 preadipocytes rapidly activates expression of CCAAT/enhancer-binding protein (C/EBP) β. Acquisition of DNA-binding activity by C/EBPβ, however, is delayed until the cells synchronously enter the S phase of mitotic clonal expansion (MCE). After MCE, C/EBPβ activates expression of C/EBPα and peroxisome proliferator-activated receptor γ, which then transcriptionally activate genes that give rise to the adipocyte phenotype. A-C/EBP, which possesses a leucine zipper but lacks functional DNA-binding and transactivation domains, forms stable inactive heterodimers with C/EBPβ in vitro. Infection of 3T3-L1 preadipocytes with an adenovirus A-C/EBP expression vector interferes with C/EBPβ function after induction of differentiation. A-C/EBP inhibited events associated with hormone-induced entry of S-phase of the cell cycle, including the turnover of p27/Kip1, a key cyclin-dependent kinase inhibitor, expression of cyclin A and cyclin-dependent kinase 2, DNA replication, MCE, and, subsequently, adipogenesis. Although A-C/EBP blocked cell proliferation associated with MCE, it did not inhibit normal proliferation of 3T3-L1 preadipocytes. Immunofluorescent staining of C/EBPβ revealed that A-C/EBP prevented the normal punctate nuclear staining of centromeres, an indicator of C/EBPβ binding to C/EBP regulatory elements in centromeric satellite DNA. The inhibitory effects of A-C/EBP appear to be due primarily to interference with nuclear import of C/EBPβ caused by obscuring its nuclear localization signal. These findings show that both MCE and adipogenesis are dependent on C/EBPβ.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.mesh3T3-L1 Cellsen_US
dc.subject.meshAdenoviridae - Geneticsen_US
dc.subject.meshAdipocytes - Cytology - Metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCcaat-Enhancer-Binding Protein-Beta - Chemistry - Metabolismen_US
dc.subject.meshCcaat-Enhancer-Binding Proteins - Chemistry - Genetics - Metabolismen_US
dc.subject.meshCell Cycleen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshCell Nucleus - Metabolismen_US
dc.subject.meshCentromere - Metabolismen_US
dc.subject.meshGenetic Vectorsen_US
dc.subject.meshMacromolecular Substancesen_US
dc.subject.meshMiceen_US
dc.subject.meshMitosisen_US
dc.subject.meshNuclear Localization Signals - Geneticsen_US
dc.subject.meshStem Cells - Cytology - Metabolismen_US
dc.titleDominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytesen_US
dc.typeArticleen_US
dc.identifier.emailZhang, JW: jzhang1@hku.hken_US
dc.identifier.authorityZhang, JW=rp01713en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.0307229101en_US
dc.identifier.pmid14688407-
dc.identifier.scopuseid_2-s2.0-0346458703en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0346458703&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume101en_US
dc.identifier.issue1en_US
dc.identifier.spage43en_US
dc.identifier.epage47en_US
dc.identifier.isiWOS:000187937200011-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhang, JW=7601339417en_US
dc.identifier.scopusauthoridTang, QQ=7201631934en_US
dc.identifier.scopusauthoridVinson, C=7004968265en_US
dc.identifier.scopusauthoridLane, MD=7401977437en_US

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