TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway

Qun Ying Lei, Heng Zhang, Bin Zhao, Zheng Yu Zha, Feng Bai, Xin-Hai Pei, Shimin Zhao, Yue Xiong, Kun Liang Guan

Research output: Contribution to journalArticle

504 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2426-2436
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number7
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Cell Proliferation
Carcinogenesis
Contact Inhibition
Serine
Hypertrophy
Drosophila
Phosphotransferases
Binding Sites
Phosphorylation
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. / Lei, Qun Ying; Zhang, Heng; Zhao, Bin; Zha, Zheng Yu; Bai, Feng; Pei, Xin-Hai; Zhao, Shimin; Xiong, Yue; Guan, Kun Liang.

In: Molecular and Cellular Biology, Vol. 28, No. 7, 01.04.2008, p. 2426-2436.

Research output: Contribution to journalArticle

Lei, Qun Ying ; Zhang, Heng ; Zhao, Bin ; Zha, Zheng Yu ; Bai, Feng ; Pei, Xin-Hai ; Zhao, Shimin ; Xiong, Yue ; Guan, Kun Liang. / TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 7. pp. 2426-2436.
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AU - Pei, Xin-Hai

AU - Zhao, Shimin

AU - Xiong, Yue

AU - Guan, Kun Liang

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