Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3
Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3
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DOI：
10.1126/science.1126313
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发表时间：
2006-05-26
期刊：
影响因子：
56.9
通讯作者：
Glimcher, Laurie H.
中科院分区：
文献类型：
--
作者：
Jones, Dallas C.;Wein, Marc N.;Glimcher, Laurie H.
基因突变破坏成骨细胞功能，可导致骨骼畸形，或更罕见的，在出生后骨形成增加。在这里，我们表明，Schnurri-3（Shn 3），哺乳动物同源的果蝇锌指适配器蛋白Shn，是一个重要的调节成人骨形成。缺乏Shn 3的小鼠表现出成年发病的骨质疏松症，由于增强的成骨细胞活性，骨量增加。Shn 3被发现控制Runx 2的蛋白水平，Runx 2是成骨细胞分化的主要转录调节因子，通过募集E3泛素连接酶WWP 1到Runx 2来促进其降解。通过这种方式，Runx 2介导的细胞外基质矿化被拮抗，揭示了Shn 3作为出生后骨量的中央调节器的重要作用。
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 osteobtast 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.