Arndt Stephanie, Poser Ina, Schubert Thomas, Moser Markus, Bosserhoff Anja-Katrin
University of Regensburg Medical School, Regensburg, Germany.
Lab Invest. 2005 Nov;85(11):1330-41. doi: 10.1038/labinvest.3700344.
The Sloan Kettering Virus (Ski) family of nuclear oncoproteins represses transforming growth factor-beta (TGF-beta) signaling through inhibition of transcriptional activity of Smad proteins. Here, we report the discovery of a new functional Smad suppressing element on chromosome 18 (Fussel-18). Fussel-18 encodes for a protein of 297 amino acids sharing characteristic structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and Ski-related novel sequence (Sno). In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage. Functionally, we determined interaction of Fussel-18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF-beta signaling. Fussel-18 is the first example of a Smad-binding protein with a highly restricted expression pattern within the nervous system.
斯隆·凯特琳病毒（Ski）家族的核癌蛋白通过抑制Smad蛋白的转录活性来抑制转化生长因子-β（TGF-β）信号传导。在此，我们报告在18号染色体上发现了一种新的功能性Smad抑制元件（Fussel-18）。Fussel-18编码一种由297个氨基酸组成的蛋白质，该蛋白质与Ski家族同源成员Ski和Ski相关新序列（Sno）具有特征性结构特征、显著同源性和相似的基因组组织。与在人类组织中普遍表达的Ski和Sno不同，原位杂交、逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法和免疫组织化学显示，Fussel-18在胚胎发育和成体阶段的神经元组织中，尤其是在小脑、脊髓和背根神经节中呈现高度特异性的表达模式。在功能上，我们确定了Fussel-18与Smad 2和Smad 3的相互作用以及对TGF-β信号传导的抑制活性。Fussel-18是神经系统内具有高度受限表达模式的Smad结合蛋白的首个实例。
