Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice
Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice
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DOI：
10.1016/j.ydbio.2004.03.003
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发表时间：
2004-06-15
影响因子：
2.7
通讯作者：
Olsen, BR
中科院分区：
文献类型：
--
作者：
Wang, WF;Wang, YG;Olsen, BR
Runx2-Cbfal是一种Run转录因子，在骨骼发育过程中发挥重要作用。它是成骨细胞分化和功能所必需的。在缺乏它的情况下，软骨细胞肥大严重受损，在骨骼发育过程中没有软骨模板的血管形成。Runx2的这些组织特异性功能可能依赖于它与其他蛋白质的相互作用。因此，我们一直在寻找可能调节Runx2活性的蛋白质。酵母双杂交系统用于鉴定Groucho同源物Grg5为Runx2相互作用蛋白。Grg5在基于细胞培养的试验中增强了Runx2的活性，通过对小鼠出生后生长的分析，我们证明了Grg5和Runx2在遗传上相互作用。我们还表明，在缺乏Grg5的情况下，Runx2单倍体功能不全导致颅缝和颧骨骨化的延迟比野生型背景下Runx2单倍体功能不全的情况更严重。最后，我们发现Runx2(+/-)Grg5(-/-)小鼠生长板中的增殖区和肥大区缩短，休息区扩大，这与IHH表达减少和印度Hedgehog(IHH)信号有关。因此，我们得出结论，Grg5在体内增强了Runx2的活性。(C)2004 Elsevier Inc.保留所有权利。
Runx2-Cbfal, a Runt transcription factor, plays important roles during skeletal development. It is required for differentiation and function of osteoblasts. In its absence, chondrocyte hypertrophy is severely impaired and there is no vascularization of cartilage templates during skeletal development. These tissue-specific functions of Runx2 are likely to be dependent on its interaction with other proteins. We have therefore searched for proteins that may modulate the activity of Runx2. The yeast two-hybrid system was used to identify a groucho homologue, Grg5, as a Runx2-interacting protein. Grg5 enhances Runx2 activity in a cell culture-based assay and by analyses of postnatal growth in mice we demonstrate that Grg5 and Runx2 interact genetically. We also show that Runx2 haploinsufficiency in the absence of Grg5 results in a more severe delay in ossification of cranial sutures and fontanels than occurs with Runx2 haploinsufficiency on a wild-type background. Finally, we find shortening of the proliferative and hypertrophic zones, and expansion of the resting zone in the growth plates of Runx2(+/-)Grg5(-/-) mice that are associated with reduced Ihh expression and Indian hedgehog (Ihh) signaling. We therefore conclude that Grg5 enhances Runx2 activity in vivo. (C) 2004 Elsevier Inc. All rights reserved.