DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGFβ pathway to regulate C. elegans dauer development
DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGFβ pathway to regulate C. elegans dauer development
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DOI：
10.1242/dev.00922
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发表时间：
2004-01-01
期刊：
影响因子：
4.6
通讯作者：
Patterson, GI
中科院分区：
文献类型：
--
作者：
da Graca, LS;Zimmerman, KK;Patterson, GI
一个非常规的tgfβ超家族通路在雄性滞育和生殖生长之间起着至关重要的作用。我们研究了daf-5基因，该基因与daf-3 Smad基因一起被上游受体和受体调节的Smad拮抗。我们发现DAF-5是与DAF-3 Smad结合的Sno/Ski超家族的新成员，这表明DAF-5与Sno/Ski一样，是TGFbeta超家族信号通路中的转录调节因子。然而，我们提出的证据表明，DAF-5是一种非常规的雪/Ski蛋白，因为DAF-5是Smad蛋白的辅助因子，而不是拮抗剂。我们发现，在神经系统中表达DAF-5可以拯救DAF-5突变体，而在肌肉或皮下表达则不能。先前的研究表明，DAF-5和DAF-3在咽肌中起调节基因表达的作用，但我们对咽特异性启动子的调节分析表明并非如此。我们提出了一个模型，其中DAF-5和DAF-3通过调节生物合成基因的表达或通过改变神经元的连接或分化状态来控制神经系统激素的产生或释放。
An unconventional TGFbeta superfamily pathway plays a crucial role in the decision between dauer diapause and reproductive growth. We have studied the daf-5 gene, which, along with the daf-3 Smad gene, is antagonized by upstream receptors and receptor-regulated Smads. We show that DAF-5 is a novel member of the Sno/Ski superfamily that binds to DAF-3 Smad, suggesting that DAF-5, like Sno/Ski, is a regulator of transcription in a TGFbeta superfamily signaling pathway. However, we present evidence that DAF-5 is an unconventional Sno/Ski protein, because DAF-5 acts as a co-factor, rather than an antagonist, of a Smad protein. We show that expressing DAF-5 in the nervous system rescues a daf-5 mutant, whereas muscle or hypodermal expression does not. Previous work suggested that DAF-5 and DAF-3 function in pharyngeal muscle to regulate gene expression, but our analysis of regulation of a pharynx specific promoter suggests otherwise. We present a model in which DAF-5 and DAF-3 control the production or release of a hormone from the nervous system by either regulating the expression of biosynthetic genes or by altering the connectivity or the differentiated state of neurons.