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    A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene

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    Authors
    Zaidi, Sayyed K.
    Javed, Amjad
    Choi, Je-Yong
    Van Wijnen, Andre J.
    Stein, Janet L.
    Lian, Jane B.
    Stein, Gary S.
    UMass Chan Affiliations
    Graduate School of Biomedical Sciences
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    2001-10-09
    Keywords
    Amino Acid Sequence; Animals; Binding Sites; Blotting, Western; Cell Nucleus; Core Binding Factor Alpha 1 Subunit; Fungal Proteins; Genes, Reporter; Hela Cells; Humans; In Situ Hybridization; Luciferases; Microscopy, Fluorescence; Molecular Sequence Data; Mutation; *Neoplasm Proteins; Osteocalcin; Plasmids; Protein Structure, Tertiary; Rats; *Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; *Signal Transduction; *Trans-Activation (Genetics); Transcription Factors; Transcription, Genetic; Tumor Cells, Cultured
    Life Sciences
    Medicine and Health Sciences
    
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    Abstract
    Key components of DNA replication and the basal transcriptional machinery as well as several tissue-specific transcription factors are compartmentalized in specialized nuclear domains. In the present study, we show that determinants of subnuclear targeting of the bone-related Runx2/Cbfa1 protein reside in the C-terminus. With a panel of C-terminal mutations, we further demonstrate that targeting of Runx2 to discrete subnuclear foci is mediated by a 38 amino acid sequence (aa 397-434). This nuclear matrix-targeting signal (NMTS) directs the heterologous Gal4 protein to nuclear-matrix-associated Runx2 foci and enhances transactivation of a luciferase gene controlled by Gal4 binding sites. Importantly, we show that targeting of Runx2 to the NM-associated foci contributes to transactivation of the osteoblast-specific osteocalcin gene in osseous cells. Taken together, these findings identify a critical component of the mechanisms mediating Runx2 targeting to subnuclear foci and provide functional linkage between subnuclear organization of Runx2 and bone-specific transcriptional control.
    Source
    J Cell Sci. 2001 Sep;114(Pt 17):3093-102. Link to article on publisher's website
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34059
    PubMed ID
    11590236
    Related Resources
    Link to Article in PubMed
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    Morningside GSBS Scholarly Publications

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