Enhanced gene activation by Notch and BMP signaling cross-talk.
The signaling systems of Notch and bone morphogenetic protein (BMP) are highly conserved from flies to mammals and have been shown to be important in the development of multiple organs. For instance, in the fate determination of mouse neuroepithelial cells, Notch signaling plays a role in keeping the progenitors from differentiating into neurons. BMP is also known to inhibit neuronal differentiation. In this paper, we show that BMP2 enhances Notch-induced transcriptional activation of Hes-5 and Hesr-1 in mouse neuroepithelial cells. BMP2 stimulation, in addition to the introduction of the intracellular domain of Notch (NIC), resulted in enhanced activation of the Hes-5 gene promoter. RBP-Jkappa binding to its target sequence is important not only for Notch signaling, but also for BMP2 signaling, to activate the Hes-5 gene promoter. Smad1, a Smad species that is activated by BMP2, barely interacted with NIC, but did form a complex with NIC in the simultaneous presence of the coactivators P/CAF and p300. Recruitment of p300 to the NIC-containing complex was facilitated by activated Smad1, which is suggested to contribute to BMP2-mediated enhancement of Notch-induced Hes-5 expression. These data suggest a novel functional cooperation between Notch signaling and BMP signaling.
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics; D050881:E1A-Associated p300 Protein; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D051548:Histone Acetyltransferases; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009687:Nuclear Proteins / Q000378:metabolism; D020239:Receptor Cross-Talk; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012097:Repressor Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C525719:Bmp2 protein, mouse; C489685:Hes5 protein, mouse; C120390:Hey protein, Drosophila; C497571:Rbpj protein, mouse; C497401:Smad1 protein, mouse; C494361:Ep300 protein, mouse