TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition
- J Biol Chem. 2009 May 15;284(20):13355-13362. doi: 10.1074/jbc.M900843200.
- 1. Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; School of Life Science Fudan University, Shanghai, China 200032.
- 2. Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032.
- 3. Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0815.
- 4. Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
- 5. Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; Department of Biological Chemistry, School of Medicine, Fudan University, Shanghai, China 200032. Electronic address: [email protected].
- 6. Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences Fudan University, Shanghai, China 200032; Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0815; Department of Biological Chemistry, School of Medicine, Fudan University, Shanghai, China 200032. Electronic address: [email protected].
The TAZ transcription co-activator has been shown to promote cell proliferation and to induce epithelial-mesenchymal transition. Recently we have demonstrated that TAZ is phosphorylated and inhibited by the Hippo tumor suppressor pathway, which is altered in human Cancer. The mechanism of TAZ-mediated transcription is unclear. We demonstrate here that TEAD is a key downstream transcription factor mediating the function of TAZ. Disruption of TEAD-TAZ binding or silencing of TEAD expression blocked the function of TAZ to promote cell proliferation and to induce epithelial-mesenchymal transition, demonstrating TEAD as a key downstream effector of TAZ. We also identified CTGF, a gene that regulates cell adhesion, proliferation, and migration, as a direct target of TAZ and TEAD. Our study establishes a functional partnership between TAZ and TEAD under negative regulation by the Hippo signaling pathway.