Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues
Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues
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DOI：
10.1038/labinvest.3700344
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发表时间：
2005-11-01
影响因子：
5
通讯作者：
Bosserhoff, AK
中科院分区：
文献类型：
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作者：
Arndt, S;Poser, I;Bosserhoff, AK
核癌蛋白的Sloan Kettering病毒（Ski）家族通过抑制Smad蛋白的转录活性来抑制转化生长因子-β（TGF-β）信号传导。在这里，我们报告发现一个新的功能Smad抑制元件18号染色体（Fussel-18）。Fussel-18编码297个氨基酸的蛋白质，与同源物Ski家族成员Ski和Ski相关的新序列（Sno）共享特征性结构特征、显著同源性和相似的基因组组织。与Ski和Sno在人体组织中广泛表达相反，原位杂交、RT-PCR、Western blot和免疫组化显示Fussel-18在胚胎发育和成体阶段的神经组织中，特别是在小脑、脊髓和背根神经节中具有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是第一个在神经系统内具有高度限制表达模式的Smad结合蛋白的例子。
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.