生物
Notch信号通路
RNA干扰
细胞生物学
细胞周期蛋白依赖激酶8
表型
转基因
基因
功能(生物学)
计算生物学
遗传学
信号转导
核糖核酸
作者
Abil Saj,Zeynep Arziman,Denise Stempfle,Werner Van Belle,Ursula Sauder,Thomas Horn,Markus Dürrenberger,Renato Paro,Michael Boutros,Gunter Merdes
标识
DOI:10.1016/j.devcel.2010.03.013
摘要
Notch signaling plays a fundamental role in cellular differentiation and has been linked to human diseases, including cancer. We report the use of comprehensive RNAi analyses to dissect Notch regulation and its connections to cellular pathways. A cell-based RNAi screen identified 900 candidate Notch regulators on a genome-wide scale. The subsequent use of a library of transgenic Drosophila expressing RNAi constructs enabled large-scale in vivo validation and confirmed 333 of 501 tested genes as Notch regulators. Mapping the phenotypic attributes of our data on an interaction network identified another 68 relevant genes and revealed several modules of unexpected Notch regulatory activity. In particular, we note an intriguing relationship to pyruvate metabolism, which may be relevant to cancer. Our study reveals a hitherto unappreciated diversity of tissue-specific modulators impinging on Notch and opens new avenues for studying Notch regulation and function in development and disease.
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