Article
- The EMBO Journal (2007) 26, 2284 - 2294
- doi:10.1038/sj.emboj.7601667
Published online: 5 April 2007
Subject Category:
CBP/p300 are bimodal regulators of Wnt signaling
Jiong Li1, Chris Sutter1, David S Parker1, Timothy Blauwkamp1, Ming Fang1,a and Ken M Cadigan1
- Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
Correspondence to:
Ken M Cadigan, Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109-1048, USA. Tel.: +1 734 936-3246; Fax: +1 734 647 0884; E-mail: cadigan@umich.edu
aPresent address: Department of Genetics and Developmental Biology, Southeast University Medical School, Nanjing 210009, China
Received 23 August 2006; Accepted 28 February 2007
Abstract
Many Wnts influence cell behavior by a conserved signaling cascade that promotes the stabilization and nuclear accumulation of 
-catenin (-cat), which then associates with TCF family members to activate target genes. The histone acetyltransferase CREB binding protein (CBP) can bind to TCF and inhibit Wnt signaling in Drosophila. In contrast, studies in vertebrates indicate a positive role for CBP and the closely related protein p300 as -cat binding transcriptional co-activators. We address this discrepancy by demonstrating that in addition to its negative role, CBP has an essential positive role in Wnt signaling in flies. CBP binds directly to the C-terminus of Armadillo (Arm, the fly -cat) and is recruited to a Wnt-regulated enhancer (WRE) in a Wnt- and Arm-dependent manner. In a human colorectal cancer cell line, we show that CBP and p300 can inhibit Wnt signaling and demonstrate that human p300 can bind directly to TCF4 in vitro. Our results argue that CBP/p300 has an evolutionarily conserved role as a buffer regulating TCF--cat/Arm binding. Subsequent to this interaction, it also has an essential role in mediating the transactivation activity of -cat/Arm.
Keywords:
- Armadillo,
- -catenin,
- CBP,
- p300,
- Wnt
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