Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein
- Ken-ichi Tago1,2,5,
- Tsutomu Nakamura1,5,
- Michiru Nishita3,
- Junko Hyodo3,
- Shin-ichi Nagai3,
- Yoji Murata1,
- Shungo Adachi1,
- Susumu Ohwada2,
- Yasuo Morishita2,
- Hiroshi Shibuya3, and
- Tetsu Akiyama1,4,6
- 1Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan; 2Second Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma 371, Japan; 3Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444, Japan; 4Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Osaka 565, Japan
Abstract
Wnt signaling has an important role in both embryonic development and tumorigenesis. β-Catenin, a key component of the Wnt signaling pathway, interacts with the TCF/LEF family of transcription factors and activates transcription of Wnt target genes. Here, we identify a novel β-catenin-interacting protein, ICAT, that was found to inhibit the interaction of β-catenin with TCF-4 and represses β-catenin–TCF-4-mediated transactivation. Furthermore, ICAT inhibited Xenopus axis formation by interfering with Wnt signaling. These results suggest that ICAT negatively regulates Wnt signaling via inhibition of the interaction between β-catenin and TCF and is integral in development and cell proliferation.
