TY - JOUR
T1 - Enhanced gene activation by Notch and BMP signaling cross-talk
AU - Takizawa, Takumi
AU - Ochiai, Wataru
AU - Nakashima, Kinichi
AU - Taga, Tetsuya
N1 - Funding Information:
We wish to thank Drs K. Miyazono, T. Honjo, R. Kageyama, P. ten Dijke, S. Itoh and U. Lendahl for kindly providing plasmid constructs. We also thank Yamanouchi Pharmaceutical Co. Ltd for providing the human recombinant BMP2. We are very grateful to Ms Y. Noguchi for her excellent secretarial assistance. We also thank Ms K. Kaneko for technical assistance. This work has been supported by a Grant-in-Aid for Scientific Research on Priority Areas and a Grant-in-Aid for 21st Century COE Research from the Ministry of Education, Culture, Sports, Science and Technology, Human Frontier Science Program, and the Virtual Research Institute of Aging of Nippon Boehringer Ingelheim.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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-Jκ 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.
AB - 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-Jκ 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.
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U2 - 10.1093/nar/gkg778
DO - 10.1093/nar/gkg778
M3 - Article
C2 - 14500836
AN - SCOPUS:0141940255
SN - 0305-1048
VL - 31
SP - 5723
EP - 5731
JO - Nucleic acids research
JF - Nucleic acids research
IS - 19
ER -