• Login
    View Item 
    •   Home
    • UMass Chan Student Research and Publications
    • Morningside Graduate School of Biomedical Sciences
    • Morningside Graduate School of Biomedical Sciences Scholarly Publications
    • View Item
    •   Home
    • UMass Chan Student Research and Publications
    • Morningside Graduate School of Biomedical Sciences
    • Morningside Graduate School of Biomedical Sciences Scholarly Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Kim, Hyo-Jin
    Nam, Soon-Hyeun
    Kim, Hyun-Jung
    Park, Hyo-Sang
    Ryoo, Hyun-Mo
    Kim, Shin-Yoon
    Cho, Tae-Joon
    Kim, Seung-Gon
    Bae, Suk-Chul
    Kim, In-San
    Stein, Janet L.
    Van Wijnen, Andre J.
    Stein, Gary S.
    Lian, Jane B.
    Choi, Je-Yong
    Show allShow less
    UMass Chan Affiliations
    Department of Biochemistry and Cell Biology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2005-11-05
    Keywords
    Adolescent; Adult; Animals; CHO Cells; Cell Nucleus; Child; Cleidocranial Dysplasia; Codon, Nonsense; Core Binding Factor Alpha 1 Subunit; Core Binding Factor beta Subunit; Cricetinae; Cytoplasm; DNA; Exons; Female; Hela Cells; Heterozygote; Humans; Male; *Mutation; Mutation, Missense; Nuclear Localization Signals; Osteocalcin; Phenotype; Promoter Regions (Genetics); Protein Binding; Protein Transport; RNA Splice Sites; Trans-Activation (Genetics); Transfection
    Life Sciences
    Medicine and Health Sciences
    
    Metadata
    Show full item record
    Link to Full Text
    http://dx.doi.org/10.1002/jcp.20552
    Abstract
    Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by haploinsufficiency of the RUNX2 gene. In this study, we analyzed by direct sequencing RUNX2 mutations from eleven CCD patients. Four of seven mutations were novel: two nonsense mutations resulted in a translational stop at codon 50 (Q50X) and 112 (E112X); a missense mutation converted arginine to glycine at codon 131 (R131G); and an exon 1 splice donor site mutation (donor splice site GT/AT, IVS1 + 1G > A) at exon 1-intron junction resulted in the deletion of QA stretch contained in exon 1 of RUNX2. We focused on the functional analysis of the IVS1 + 1G > A mutation. A full-length cDNA of this mutation was cloned (RUNX2Deltae1) and expressed in Chinese hamster ovary (CHO) and HeLa cells. Functional analysis of RUNX2Deltae1 was performed with respect to protein stability, nuclear localization, DNA binding, and transactivation activity of a downstream RUNX2 target gene. Protein stability of RUNX2Deltae1 is similar to wild-type RUNX2 as determined by Western blot analysis. Subcellular localization of RUNX2Deltae1, assessed by in situ immunofluorescent staining, was observed with partial retention in both the nucleus and cytoplasm. This finding is in contrast to RUNX2 wild-type, which is detected exclusively in the nucleus. DNA binding activity was also compromised by the RUNX2Deltae1 in gel shift assay. Finally, RUNX2Deltae1 blocked transactivation of the osteocalcin gene determined by transient transfection assay. Our findings demonstrate for the first time that the CCD phenotype can be caused by a splice site mutation, which results in the deletion of N-terminus amino acids containing the QA stretch in RUNX2 that contains a previously unidentified second nuclear localization signal (NLS). We postulate that the QA sequence unique to RUNX2 contributes to a competent structure of RUNX2 that is required for nuclear localization, DNA binding, and transactivation function.
    Source
    J Cell Physiol. 2006 Apr;207(1):114-22. Link to article on publisher's site
    DOI
    10.1002/jcp.20552
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33949
    PubMed ID
    16270353
    Related Resources
    Link to article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/jcp.20552
    Scopus Count
    Collections
    Morningside Graduate School of Biomedical Sciences Scholarly Publications

    entitlement

    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.