Laboratory of Molecular Biology (Celgen) of Center for Human Genetics, University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Cytokine Growth Factor Rev. 2011 Oct-Dec;22(5-6):287-300. doi: 10.1016/j.cytogfr.2011.11.006. Epub 2011 Nov 26.
Signaling by the many ligands of the TGFβ family strongly converges towards only five receptor-activated, intracellular Smad proteins, which fall into two classes i.e. Smad2/3 and Smad1/5/8, respectively. These Smads bind to a surprisingly high number of Smad-interacting proteins (SIPs), many of which are transcription factors (TFs) that co-operate in Smad-controlled target gene transcription in a cell type and context specific manner. A combination of functional analyses in vivo as well as in cell cultures and biochemical studies has revealed the enormous versatility of the Smad proteins. Smads and their SIPs regulate diverse molecular and cellular processes and are also directly relevant to development and disease. In this survey, we selected appropriate examples on the BMP-Smads, with emphasis on Smad1 and Smad5, and on a number of SIPs, i.e. the CPSF subunit Smicl, Ttrap (Tdp2) and Sip1 (Zeb2, Zfhx1b) from our own research carried out in three different vertebrate models.
TGFβ 家族的许多配体通过信号传导强烈汇聚到仅五种受体激活的细胞内 Smad 蛋白，这些蛋白分为两类，即 Smad2/3 和 Smad1/5/8。这些 Smad 蛋白与大量的 Smad 相互作用蛋白（SIP）结合，其中许多是转录因子（TF），它们以细胞类型和上下文特异性的方式在 Smad 控制的靶基因转录中合作。体内功能分析以及细胞培养和生化研究的结合揭示了 Smad 蛋白的巨大多功能性。Smads 及其 SIP 调节多种分子和细胞过程，并且与发育和疾病直接相关。在本综述中，我们选择了 BMP-Smads 的适当例子，重点是 Smad1 和 Smad5，以及一些 SIP，即来自我们在三个不同脊椎动物模型中进行的自身研究的 CPSF 亚基 Smicl、Ttrap（Tdp2）和 Sip1（Zeb2、Zfhx1b）。
