IngentaConnect Enhanced gene activation by Notch and BMP signaling cross-talk

Authors: Takumi Takizawa¹; Wataru Ochiai¹; Kinichi Nakashima¹; Tetsuya Taga²

Source: Nucleic Acids Research, Volume 31, Number 19, 01 October 2003 , pp. 5723-5731(9)

Abstract:

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-J kappa

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.

Document Type: Research article

DOI: 10.1093/nar/gkg778

Affiliations: 1: Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan and 2: *To whom correspondence should be addressed. Tel taga@kaiju.medic.kumamoto-u.ac.jp, Fax: +81 96 373 6610