Schnurri-3: A key regulator of postnatal skeletal remodeling
Schnurri-3: A key regulator of postnatal skeletal remodeling
复制标题
DOI：
10.1109/oceans.2007.4449207
复制
发表时间：
2007-01-01
期刊：
影响因子：
--
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.
Schnurri-3是一种与果蝇Shn亲缘关系较远的大型锌指蛋白，是成年骨形成的有效和必要的调节剂。缺乏Shn 3的小鼠表现出成骨细胞表型，由于成骨细胞活性增强，骨量显著增加。Shn 3通过促进Runx 2的降解来控制Runx 2的蛋白水平，Runx 2是成骨细胞分化的主要调节因子。在成骨细胞中，Shn 3作为Runx 2和E3泛素连接酶WWP 1之间的三聚体复合物的组分发挥作用。该复合物抑制Runx 2功能和参与细胞外基质矿化的基因的表达，这是由于WWP 1能够促进Runx 2多聚泛素化和蛋白酶体依赖性降解。我们的研究揭示了Shn 3作为出生后骨量调节剂的重要作用。设计用于阻断Shn 3/WWP 1功能的化合物可能是用于治疗骨质疏松症的可能治疗剂。
Schnurri-3, a large zinc finger protein distantly related to Drosophila Shn, is a potent and essential regulator of adult bone formation. Mice lacking Shn3 display an osteosclerotic phenotype with profoundly increased bone mass due to augmented osteoblast activity. Shn3 controls protein levels of Runx2, the principal regulator of osteoblast differentiation, by promoting its degradation. In osteoblasts, Shn3 functions as a component of a trimeric complex between Runx2 and the E3 ubiquitin ligase WWP1. This complex inhibits Runx2 function and expression of genes involved in extracellular matrix mineralization due to the ability of WWP1 to promote Runx2 polyubiquitination and proteasome-dependent degradation. Our study reveals an essential role for Shn3 as a regulator of postnatal bone mass. Compounds designed to block Shn3/WWP1 function may be possible therapeutic agents for the treatment of osteoporosis.