ZFP423 coordinates Notch and bone morphogenetic protein signaling, selectively up-regulating Hes5 gene expression.
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.
Masserdotti
Giacomo
G
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
Badaloni
Aurora
A
Green
Yangsook Song
YS
Croci
Laura
L
Barili
Valeria
V
Bergamini
Giorgio
G
Vetter
Monica L
ML
Consalez
G Giacomo
GG
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D051379:Mice; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D029867:Xenopus Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D004268:DNA-Binding Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C525810:Bmp4 protein, mouse; C484557:Ebfaz protein, mouse; C504431:Esr1 protein, Xenopus; C489685:Hes5 protein, mouse; C497762:Notch1 protein, mouse; C525812:bmp4 protein, Xenopus