File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Transcriptional regulation of mitotic checkpoint gene MAD1 by p53

TitleTranscriptional regulation of mitotic checkpoint gene MAD1 by p53
Authors
Issue Date2003
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2003, v. 278 n. 39, p. 37439-37450 How to Cite?
Abstractp53 regulates a number of genes through transcriptional activation and repression. p53-dependent mitotic checkpoint has been described, but the underlying mechanism is still obscure. Here we examined the effect of p53 on the expression of a human mitotic checkpoint protein, Mitosis Arrest Deficiency 1 (MAD1), in cultured human cells. The expression of MAD1 was reduced when the cells were overexpressing exogenously introduced wild-type p53. The same reduction was also observed when the cells were treated with anticancer agents 5-fluorouracil and cisplatin or were irradiated with UV. Consistently, MAD1 promoter activity diminished in a dose-dependent manner when induced by p53, indicating that p53 repressed MAD1 at a transcriptional level. Intriguingly, several tumor hot spot mutations in p53 (V143A, R175H, R248W, and R273H) did not abolish the ability of p53 to repress MAD1 expression. By serial truncation of the MAD1 promoter, we confined the p53-responsive element to a 38-bp region that represents a novel sequence distinct from the known p53 consensus binding site. Trichostatin A, a histone deacetylase inhibitor, relieved the p53 transrepression activity on MAD1. Chromatin immunoprecipitation assay revealed that p53, histone deacetylase 1, and co-repressor mSin3a associated with the MAD1 promoter in vivo. Taken together, our findings suggest a regulatory mechanism for the mitotic checkpoint in which MAD1 is inhibited by p53.
Persistent Identifierhttp://hdl.handle.net/10722/68339
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChun, ACSen_HK
dc.contributor.authorJin, DYen_HK
dc.date.accessioned2010-09-06T06:03:39Z-
dc.date.available2010-09-06T06:03:39Z-
dc.date.issued2003en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2003, v. 278 n. 39, p. 37439-37450en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68339-
dc.description.abstractp53 regulates a number of genes through transcriptional activation and repression. p53-dependent mitotic checkpoint has been described, but the underlying mechanism is still obscure. Here we examined the effect of p53 on the expression of a human mitotic checkpoint protein, Mitosis Arrest Deficiency 1 (MAD1), in cultured human cells. The expression of MAD1 was reduced when the cells were overexpressing exogenously introduced wild-type p53. The same reduction was also observed when the cells were treated with anticancer agents 5-fluorouracil and cisplatin or were irradiated with UV. Consistently, MAD1 promoter activity diminished in a dose-dependent manner when induced by p53, indicating that p53 repressed MAD1 at a transcriptional level. Intriguingly, several tumor hot spot mutations in p53 (V143A, R175H, R248W, and R273H) did not abolish the ability of p53 to repress MAD1 expression. By serial truncation of the MAD1 promoter, we confined the p53-responsive element to a 38-bp region that represents a novel sequence distinct from the known p53 consensus binding site. Trichostatin A, a histone deacetylase inhibitor, relieved the p53 transrepression activity on MAD1. Chromatin immunoprecipitation assay revealed that p53, histone deacetylase 1, and co-repressor mSin3a associated with the MAD1 promoter in vivo. Taken together, our findings suggest a regulatory mechanism for the mitotic checkpoint in which MAD1 is inhibited by p53.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshBasic Helix-Loop-Helix Transcription Factorsen_HK
dc.subject.meshCell Cycle Proteinsen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshGene Expression Regulationen_HK
dc.subject.meshGenes, cdcen_HK
dc.subject.meshHistone Deacetylase 1en_HK
dc.subject.meshHistone Deacetylases - physiologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHydroxamic Acids - pharmacologyen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshNuclear Proteinsen_HK
dc.subject.meshPhosphoproteins - geneticsen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshRepressor Proteins - genetics - physiologyen_HK
dc.subject.meshResponse Elementsen_HK
dc.subject.meshTranscription Factors - physiologyen_HK
dc.subject.meshTranscription, Geneticen_HK
dc.subject.meshTumor Suppressor Protein p53 - physiologyen_HK
dc.titleTranscriptional regulation of mitotic checkpoint gene MAD1 by p53en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=278&issue=39&spage=37439&epage=37450&date=2003&atitle=Transcriptional+regulation+of+mitotic+checkpoint+gene+MAD1+by+p53en_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M307185200en_HK
dc.identifier.pmid12876282-
dc.identifier.scopuseid_2-s2.0-0141733191en_HK
dc.identifier.hkuros83712en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0141733191&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume278en_HK
dc.identifier.issue39en_HK
dc.identifier.spage37439en_HK
dc.identifier.epage37450en_HK
dc.identifier.isiWOS:000185437200056-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChun, ACS=7003650706en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats