近期科学家们发现了一组独特的基因，它们在肌肉细胞分化中发挥重要作用，或可为防止肌肉癌症蔓延提供新的治疗靶标。研究人员分析发现Smad7和β-catenin蛋白在体内协同工作从而调节肌细胞分化、生长和修复。该研究结果发表Cell Death & Disease杂志上。
Smad7和β-catenin复合物功能失调会导致肌细胞分化受损，这是一些软组织肿瘤的标志，如横纹肌肉瘤。横纹肌肉瘤细胞从功能和表型来看，与肌肉细胞一样，但区别在于它们不会停止分裂，可以在身体的不同部位形成肿瘤。于是，科学家提出假设：这些细胞的分化程序出现缺陷的部分原因是由于控制β-catenin复合物的信号通路异常而被降解。如果能使β-catenin和Smad7复合物稳定，意味着可以阻止这些细胞形成肿瘤。因此，研究团队重点研究了解转录因子在组织特异性基因表达和分化中的作用，通过识别在肌肉发育过程中参与转录调控的DNA结合蛋白来实现这个目的。
该研究还发现了新的肌肉再生调节因子，这为解决正常但虚弱老年人群的肌肉流失问题提供了方向，也为肌肉萎缩和癌症的治疗干预确定了新的分子靶点。
推荐阅读原文：
Smad7:β-catenin complex regulates myogenic gene transcription.
Recent reports indicate that Smad7 promotes skeletal muscle differentiation and growth. We previously documented a non-canonical role of nuclear Smad7 during myogenesis, independent of its role in TGF-β signaling. Here further characterization of the myogenic function of Smad7 revealed β-catenin as a Smad7 interacting protein. Biochemical analysis identified a Smad7 interaction domain (SID) between aa575 and aa683 of β-catenin. Reporter gene analysis and chromatin immunoprecipitation demonstrated that Smad7 and β-catenin are cooperatively recruited to the extensively characterized ckm promoter proximal region to facilitate its muscle restricted transcriptional activation in myogenic cells. Depletion of endogenous Smad7 and β-catenin in muscle cells reduced ckm promoter activity indicating their role during myogenesis. Deletion of the β-catenin SID substantially reduced the effect of Smad7 on the ckm promoter and exogenous expression of SID abolished β-catenin function, indicating that SID functions as a trans dominant-negative regulator of β-catenin activity. β-catenin interaction with the Mediator kinase complex through its Med12 subunit led us to identify MED13 as an additional Smad7-binding partner. Collectively, these studies document a novel function of a Smad7-MED12/13-β-catenin complex at the ckm locus, indicating a key role of this complex in the program of myogenic gene expression underlying skeletal muscle development and regeneration.
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