TEAD Transcription Factors Mediate the Function of TAZ in Cell Growth and Epithelial-Mesenchymal Transition*
- Heng Zhang‡§,1,
- Chen-Ying Liu‡§,1,
- Zheng-Yu Zha‡,
- Bin Zhao¶,
- Jun Yao‡,
- Shimin Zhao‡§,
- Yue Xiong‡∥,
- Qun-Ying Lei‡,**,2 and
- Kun-Liang Guan‡¶,**,3
- ‡Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, §School of Life Science, and **Department of Biological Chemistry, School of Medicine, Fudan University, Shanghai, China 200032, ¶Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0815, and ∥Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599
- ↵2 To whom correspondence may be addressed: qlei{at}fudan.edu.cn. 3 To whom correspondence may be addressed: kuguan{at}ucsd.edu.
Abstract
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.
Footnotes
-
↵* This work was supported, in whole or in part, by National Institutes of Health grants RO1CA65572 and RO1CA132809 (to Y. X. and K.-L. G.). This work was also supported by 985 Program from the Chinese Ministry of Education, National High Technology Research and Development Program of China Grants 2004BA711A18 and 2006AA02A308, State Key Development Program for Basic Research of China Grants 2006CB806700 and 2009CB918401, National Natural Science Foundation of China Grants 30600112 and 30871255, Shanghai Key Project Grant 06JC14086, Pufa Talent Grant 07pj14011, Shanghai Leading Academic Discipline Project, project number B110, and a University of Michigan Rackham predoctoral fellowship (to B. Z.).
-
↵
The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1 and Table 1.
-
↵1 Both authors contributed equally to this work.
- Received February 5, 2009.
- Revision received March 26, 2009.
- The American Society for Biochemistry and Molecular Biology, Inc.
