Article
- The EMBO Journal (2001) 20, 4500 - 4511
- doi:10.1093/emboj/20.16.4500
Negative regulation of the Wnt–
-catenin pathway by the transcriptional repressor HBP1
Ellen M. Sampson1, Zaffar K. Haque1, Man-Ching Ku1, Sergei G. Tevosian1,2, Chris Albanese3, Richard G. Pestell3, K.Eric Paulson1 and Amy S. Yee1
- Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
- Present address: Department of Genetics, Dartmouth University, Hanover, NH 03755, USA
- The Albert Einstein Cancer Center, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Correspondence to:
Amy S. Yee, E-mail: amy.yee@tufts.edu
Received 16 March 2001; Accepted 27 June 2001; Revised 18 June 2001
Abstract
In certain cancers, constitutive Wnt signaling results from mutation in one or more pathway components. The result is the accumulation and nuclear localization of 
-catenin, which interacts with the lymphoid enhancer factor-1 (LEF)/T-cell factor (TCF) family of HMG-box transcription factors, which activate important growth regulatory genes, including cyclin D1 and c-myc. As exemplified by APC and axin, the negative regulation of -catenin is important for tumor suppression. Another potential mode of negative regulation is transcriptional repression of cyclin D1 and other Wnt target genes. In mammals, the transcriptional repressors in the Wnt pathway are not well defined. We have previously identified HBP1 as an HMG-box repressor and a cell cycle inhibitor. Here, we show that HBP1 is a repressor of the cyclin D1 gene and inhibits the Wnt signaling pathway. The inhibition of Wnt signaling and growth requires a common domain of HBP1. The apparent mechanism is an inhibition of TCF/LEF DNA binding through a physical interaction with HBP1. These data suggest that the suppression of Wnt signaling by HBP1 may be a mechanism to prevent inappropriate proliferation.
Keywords:
- -catenin,
- HBP1,
- HMG-box transcription factor,
- Wnt
