Kankel Mark W, Hurlbut Gregory D, Upadhyay Geeta, Yajnik Vijay, Yedvobnick Barry, Artavanis-Tsakonas Spyros
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Genetics. 2007 Dec;177(4):2493-505. doi: 10.1534/genetics.107.080994.
Notch signaling regulates multiple developmental processes and is implicated in various human diseases. Through use of the Notch transcriptional co-activator mastermind, we conducted a screen for Notch signal modifiers using the Exelixis collection of insertional mutations, which affects approximately 50% of the Drosophila genome, recovering 160 genes never before associated with Notch, extending the previous roster of genes that interact functionally with the Notch pathway and mastermind. As the molecular identity for most recovered genes is known, gene ontology (GO) analysis was applied, grouping genes according to functional classifications. We identify novel Notch-associated GO categories, uncover nodes of integration between Notch and other signaling pathways, and unveil groups of modifiers that suggest the existence of Notch-independent mastermind functions, including a conserved ability to regulate Wnt signaling.
Notch信号通路调控多种发育过程，并与多种人类疾病相关。通过使用Notch转录共激活因子mastermind，我们利用Exelixis插入突变文库对Notch信号调节因子进行了筛选，该文库影响了约50%的果蝇基因组，从中发现了160个以前从未与Notch相关的基因，扩展了先前与Notch信号通路和mastermind在功能上相互作用的基因列表。由于大多数发现基因的分子身份已知，因此应用了基因本体（GO）分析，根据功能分类对基因进行分组。我们识别出了新的与Notch相关的GO类别，揭示了Notch与其他信号通路之间的整合节点，并发现了一些调节因子组，这表明存在不依赖Notch的mastermind功能，包括调节Wnt信号通路的保守能力。
