TAZ Promotes Cell Proliferation and Epithelial-Mesenchymal Transition and Is Inhibited by the Hippo Pathway
Top Cited Papers
- 1 April 2008
- journal article
- research article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 28 (7) , 2426-2436
- https://doi.org/10.1128/mcb.01874-07
Abstract
TAZ is a WW domain containing a transcription coactivator that modulates mesenchymal differentiation and development of multiple organs. In this study, we show that TAZ is phosphorylated by the Lats tumor suppressor kinase, a key component of the Hippo pathway, whose alterations result in organ and tissue hypertrophy in Drosophila and contribute to tumorigenesis in humans. Lats phosphorylates TAZ on several serine residues in the conserved HXRXXS motif and creates 14-3-3 binding sites, leading to cytoplasmic retention and functional inactivation of TAZ. Ectopic expression of TAZ stimulates cell proliferation, reduces cell contact inhibition, and promotes epithelial-mesenchymal transition (EMT). Elimination of the Lats phosphorylation sites results in a constitutively active TAZ, enhancing the activity of TAZ in promoting cell proliferation and EMT. Our results elucidate a molecular mechanism for TAZ regulation and indicate a potential function of TAZ as an important target of the Hippo pathway in regulating cell proliferation tumorigenesis.Keywords
This publication has 39 references indexed in Scilit:
- Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth controlGenes & Development, 2007
- TAZ Promotes PC2 Degradation through a SCFβ-Trcp E3 Ligase ComplexMolecular and Cellular Biology, 2007
- RASSF1A Elicits Apoptosis through an MST2 Pathway Directing Proapoptotic Transcription by the p73 Tumor Suppressor ProteinMolecular Cell, 2007
- Elucidation of a Universal Size-Control Mechanism in Drosophila and MammalsCell, 2007
- Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in DrosophilaThe EMBO Journal, 2007
- Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1Proceedings of the National Academy of Sciences, 2007
- Transforming properties of YAP , a candidate oncogene on the chromosome 11q22 ampliconProceedings of the National Academy of Sciences, 2006
- The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAPCell, 2005
- Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor, MatsCell, 2005
- salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell LinesCell, 2002