ZFP423 Coordinates Notch and Bone Morphogenetic Protein Signaling, Selectively Up-regulating Hes5 Gene Expression
ZFP423 Coordinates Notch and Bone Morphogenetic Protein Signaling, Selectively Up-regulating Hes5 Gene Expression
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DOI：
10.1074/jbc.m110.142869
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发表时间：
2010-10-01
影响因子：
4.8
通讯作者：
Consalez, G. Giacomo
中科院分区：
文献类型：
--
作者：
Masserdotti, Giacomo;Badaloni, Aurora;Consalez, G. Giacomo
锌指蛋白423编码一个参与小脑和嗅觉发育的锌指转录因子。ZFP 423是SMAD 1-SMAD 4和Collier/Olf-1/EBF蛋白的已知相互作用物，并且充当视黄酸诱导的分化的修饰剂。在这篇文章中，我们发现ZFP 423与Notch 1在哺乳动物细胞系和非洲爪蟾神经胚中的胞内结构域相互作用，以激活Notch 1靶点Hes 5/ESR 1的表达。这种作用被EBF转录因子拮抗，无论是在培养的细胞和非洲爪蟾胚胎，并在体外扩增BMP 4，表明ZFP 423的行为整合BMP和Notch信号，选择性地促进其收敛到Hes 5基因启动子。
Zinc finger protein 423 encodes a 30 Zn-finger transcription factor involved in cerebellar and olfactory development. ZFP423 is a known interactor of SMAD1-SMAD4 and of Collier/Olf-1/EBF proteins, and acts as a modifier of retinoic acid-induced differentiation. In the present article, we show that ZFP423 interacts with the Notch1 intracellular domain in mammalian cell lines and in Xenopus neurula embryos, to activate the expression of the Notch1 target Hes5/ESR1. This effect is antagonized by EBF transcription factors, both in cultured cells and in Xenopus embryos, and amplified in vitro by BMP4, suggesting that ZFP423 acts to integrate BMP and Notch signaling, selectively promoting their convergence onto the Hes5 gene promoter.