Department of Cell Biology; Graduate School of Biomedical Sciences
Medical Subject Headings
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
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.
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Citation: J Cell Sci. 2001 Sep;114(Pt 17):3093-102. Link to article on publisher's website