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Article: Bridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription

TitleBridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription
Authors
Issue Date1999
PublisherAmerican Society for Microbiology.
Citation
Molecular And Cellular Biology, 1999, v. 19 n. 12, p. 8492-8504 How to Cite?
AbstractProteins in the E2A family of basic helix-loop-helix transcription factors are important in a wide spectrum of physiologic processes as diverse as neurogenesis, myogenesis, lymphopoeisis, and sex determination. In the pancreatic β cell, E2A proteins, in combination with tissue-specific transcription factors, regulate expression of the insulin gene and other genes critical for β-cell function. By yeast two-hybrid screening of a cDNA library prepared from rat insulinoma (INS-1) cells, we identified a novel protein, Bridge-1, that interacts with E2A proteins and functions as a coactivator of gene transcription mediated by E12 and E47. Bridge-1 contains a PDZ-like domain, a domain known to be involved in protein-protein interactions. Bridge-1 is highly expressed in pancreatic islets and islet cell lines and the expression pattern is primarily nuclear. The interaction of Bridged with E2A proteins is further demonstrated by coimmunoprecipitation of in vitro-translated Bridged with E12 or E47 and by mammalian two-hybrid studies. The PDZ-like domain of Bridged is required for interaction with the carboxy terminus of E12. In both yeast and mammalian two-hybrid interaction studies, Bridge-1 mutants lacking an intact PDZ-like domain interact poorly with E12. An E12 mutant (E12ΔC) lacking the carboxy-terminal nine amino acids shows impaired interaction with Bridge-1. Bridge-1 has direct transactivational activity, since a Gal4 DNA-binding domain-Bridge-1 fusion protein transactivates a Gal4CAT reporter. Bridge-1 also functions as a coactivator by enhancing E12- or E47-mediated activation of a rat insulin I gene minienhancer promoter-reporter construct in transient-transfection experiments. Substitution of the mutant E12ΔC for E12 reduces the coactivation of the rat insulin I minienhancer by Bridge-1. Inactivation of endogenous Bridge-1 in insulinoma (INS-1) cells by expression of a Bridged antisense RNA diminishes rat insulin I promoter activity. Bridge-1, by utilizing its PDZ-like domain to interact with E12, may provide a new mechanism for the coactivation and regulation of transcription of the insulin gene.
Persistent Identifierhttp://hdl.handle.net/10722/48977
ISSN
2015 Impact Factor: 4.427
2015 SCImago Journal Rankings: 3.806
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorThomas, MKen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorTenser, MSen_HK
dc.contributor.authorWong, GGen_HK
dc.contributor.authorHabener, JFen_HK
dc.date.accessioned2008-06-12T06:31:13Z-
dc.date.available2008-06-12T06:31:13Z-
dc.date.issued1999en_HK
dc.identifier.citationMolecular And Cellular Biology, 1999, v. 19 n. 12, p. 8492-8504en_HK
dc.identifier.issn0270-7306en_HK
dc.identifier.urihttp://hdl.handle.net/10722/48977-
dc.description.abstractProteins in the E2A family of basic helix-loop-helix transcription factors are important in a wide spectrum of physiologic processes as diverse as neurogenesis, myogenesis, lymphopoeisis, and sex determination. In the pancreatic β cell, E2A proteins, in combination with tissue-specific transcription factors, regulate expression of the insulin gene and other genes critical for β-cell function. By yeast two-hybrid screening of a cDNA library prepared from rat insulinoma (INS-1) cells, we identified a novel protein, Bridge-1, that interacts with E2A proteins and functions as a coactivator of gene transcription mediated by E12 and E47. Bridge-1 contains a PDZ-like domain, a domain known to be involved in protein-protein interactions. Bridge-1 is highly expressed in pancreatic islets and islet cell lines and the expression pattern is primarily nuclear. The interaction of Bridged with E2A proteins is further demonstrated by coimmunoprecipitation of in vitro-translated Bridged with E12 or E47 and by mammalian two-hybrid studies. The PDZ-like domain of Bridged is required for interaction with the carboxy terminus of E12. In both yeast and mammalian two-hybrid interaction studies, Bridge-1 mutants lacking an intact PDZ-like domain interact poorly with E12. An E12 mutant (E12ΔC) lacking the carboxy-terminal nine amino acids shows impaired interaction with Bridge-1. Bridge-1 has direct transactivational activity, since a Gal4 DNA-binding domain-Bridge-1 fusion protein transactivates a Gal4CAT reporter. Bridge-1 also functions as a coactivator by enhancing E12- or E47-mediated activation of a rat insulin I gene minienhancer promoter-reporter construct in transient-transfection experiments. Substitution of the mutant E12ΔC for E12 reduces the coactivation of the rat insulin I minienhancer by Bridge-1. Inactivation of endogenous Bridge-1 in insulinoma (INS-1) cells by expression of a Bridged antisense RNA diminishes rat insulin I promoter activity. Bridge-1, by utilizing its PDZ-like domain to interact with E12, may provide a new mechanism for the coactivation and regulation of transcription of the insulin gene.en_HK
dc.format.extent384 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology.en_HK
dc.relation.ispartofMolecular and Cellular Biologyen_HK
dc.rightsMolecular and Cellular Biology. Copyright © American Society for Microbiology.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsCopyright © American Society for Microbiology, Molecular and Cellular Biology, 1999, v. 19 n. 12, p. 8492-8504en_HK
dc.subject.meshDNA-Binding Proteins - genetics - metabolismen_HK
dc.subject.meshHelix-Loop-Helix Motifsen_HK
dc.subject.meshInsulin - geneticsen_HK
dc.subject.meshPromoter Regions (Genetics)en_HK
dc.subject.meshTrans-Activation (Genetics)en_HK
dc.titleBridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcriptionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-7306&volume=19&issue=12&spage=8492&epage=8504&date=1999&atitle=Bridge-1,+a+novel+PDZ-domain+coactivator+of+E2A-mediated+regulation+of+insulin+gene+transcriptionen_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid10567574-
dc.identifier.pmcidPMC84960en_HK
dc.identifier.scopuseid_2-s2.0-0033499802en_HK
dc.identifier.hkuros52606-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033499802&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue12en_HK
dc.identifier.spage8492en_HK
dc.identifier.epage8504en_HK
dc.identifier.isiWOS:000083781300059-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridThomas, MK=7404754193en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridTenser, MS=6507376771en_HK
dc.identifier.scopusauthoridWong, GG=7402527602en_HK
dc.identifier.scopusauthoridHabener, JF=7102415950en_HK

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