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Article: Role of a novel splice variant of mitotic arrest deficient 1 (MAD1), MAD1β, in mitotic checkpoint control in liver cancer

TitleRole of a novel splice variant of mitotic arrest deficient 1 (MAD1), MAD1β, in mitotic checkpoint control in liver cancer
Authors
Issue Date2008
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2008, v. 68 n. 22, p. 9194-9201 How to Cite?
AbstractLoss of mitotic checkpoint contributes to chromosomal instability, leading to carcinogenesis. In this study, we identified a novel splicing variant of mitotic arrest deficient 1 (MAD1), designated MAD1β, and investigated its role in mitotic checkpoint control in hepatocellular carcinoma (HCC). The expression levels of human MAD1β were examined in hepatoma cell lines and human HCC samples. The functional roles of MAD1β in relation to the mitotic checkpoint control, chromosomal instability, and binding with MAD2 were assessed in hepatoma cell lines. On sequencing, MAD1β was found to have deletion of exon 4. It was expressed at both mRNA and protein levels in the nine hepatoma cell lines tested and was overexpressed in 12 of 50 (24%) human HCCs. MAD1β localized in the cytoplasm, whereas MAD1α was found in the nucleus. This cytoplasmic localization of MAD1β was due to the absence of a nuclear localization signal in MAD1α. In addition, MAD1β was found to physically interact with MAD2 and sequester it in the cytoplasm. Furthermore, expression of MAD1β induced mitotic checkpoint impairment, chromosome bridge formation, and aberrant chromosome numbers via binding with MAD2. Our data suggest that the novel splicing variant MAD1β may have functions different from those of MAD1α and may play opposing roles to MAD1α in mitotic checkpoint control in hepatocarcinogenesis. ©2008 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/147593
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong ResearchHKU 7454/03M
Research Grants Council Collaborative Research FundHKU 1/06C
Funding Information:

Grant support: Hong Kong Research Grants Council General Research Fund (HKU 7454/03M) and Research Grants Council Collaborative Research Fund (HKU 1/06C). I.O-L. Ng is Loke Yew Professor in Pathology.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorSze, KMFen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2012-05-29T06:04:50Z-
dc.date.available2012-05-29T06:04:50Z-
dc.date.issued2008en_HK
dc.identifier.citationCancer Research, 2008, v. 68 n. 22, p. 9194-9201en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/147593-
dc.description.abstractLoss of mitotic checkpoint contributes to chromosomal instability, leading to carcinogenesis. In this study, we identified a novel splicing variant of mitotic arrest deficient 1 (MAD1), designated MAD1β, and investigated its role in mitotic checkpoint control in hepatocellular carcinoma (HCC). The expression levels of human MAD1β were examined in hepatoma cell lines and human HCC samples. The functional roles of MAD1β in relation to the mitotic checkpoint control, chromosomal instability, and binding with MAD2 were assessed in hepatoma cell lines. On sequencing, MAD1β was found to have deletion of exon 4. It was expressed at both mRNA and protein levels in the nine hepatoma cell lines tested and was overexpressed in 12 of 50 (24%) human HCCs. MAD1β localized in the cytoplasm, whereas MAD1α was found in the nucleus. This cytoplasmic localization of MAD1β was due to the absence of a nuclear localization signal in MAD1α. In addition, MAD1β was found to physically interact with MAD2 and sequester it in the cytoplasm. Furthermore, expression of MAD1β induced mitotic checkpoint impairment, chromosome bridge formation, and aberrant chromosome numbers via binding with MAD2. Our data suggest that the novel splicing variant MAD1β may have functions different from those of MAD1α and may play opposing roles to MAD1α in mitotic checkpoint control in hepatocarcinogenesis. ©2008 American Association for Cancer Research.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshCalcium-Binding Proteins - Physiologyen_US
dc.subject.meshCarcinoma, Hepatocellular - Pathologyen_US
dc.subject.meshCell Cycle Proteins - Analysis - Genetics - Physiologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Nucleus - Chemistryen_US
dc.subject.meshChromosomal Instabilityen_US
dc.subject.meshChromosome Aberrationsen_US
dc.subject.meshCytoplasm - Chemistryen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver Neoplasms - Pathologyen_US
dc.subject.meshMitosisen_US
dc.subject.meshNuclear Proteins - Analysis - Genetics - Physiologyen_US
dc.subject.meshProtein Isoformsen_US
dc.subject.meshRna, Messenger - Analysisen_US
dc.subject.meshRepressor Proteins - Physiologyen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.titleRole of a novel splice variant of mitotic arrest deficient 1 (MAD1), MAD1β, in mitotic checkpoint control in liver canceren_HK
dc.typeArticleen_HK
dc.identifier.emailChing, YP:ypching@hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.emailSze, MF: szekaren@yahoo.com-
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-08-2600en_HK
dc.identifier.pmid19010891-
dc.identifier.scopuseid_2-s2.0-56449096184en_HK
dc.identifier.hkuros154362-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56449096184&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume68en_HK
dc.identifier.issue22en_HK
dc.identifier.spage9194en_HK
dc.identifier.epage9201en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000261136600014-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.relation.projectDeciphering dysregulation of mitotic checkpoint control in liver cancer-
dc.identifier.scopusauthoridSze, KMF=36828094800en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK

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