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    Science. 2006 May 26;312(5777):1223-7.

    Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3.

    Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH.

    Source

    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

    Abstract

    Genetic mutations that disrupt osteoblast function can result in skeletal dysmorphogenesis or, more rarely, in increased postnatal bone formation. Here we show that Schnurri-3 (Shn3), a mammalian homolog of the Drosophila zinc finger adapter protein Shn, is an essential regulator of adult bone formation. Mice lacking Shn3 display adult-onset osteosclerosis with increased bone mass due to augmented osteoblast activity. Shn3 was found to control protein levels of Runx2, the principal transcriptional regulator of osteoblast differentiation, by promoting its degradation through recruitment of the E3 ubiquitin ligase WWP1 to Runx2. By this means, Runx2-mediated extracellular matrix mineralization was antagonized, revealing an essential role for Shn3 as a central regulator of postnatal bone mass.

    PMID:
    16728642
    [PubMed - indexed for MEDLINE]

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