PARD3 induces TAZ activation and cell growth by promoting LATS1 and PP1 interaction

Xian-Bo Lv; Chen-Ying Liu; Zhen Wang; Yi-Ping Sun; Yue Xiong; Qun-Ying Lei; Kun-Liang Guan

doi:10.15252/embr.201439951

PARD3 induces TAZ activation and cell growth by promoting LATS1 and PP1 interaction

EMBO Rep. 2015 Aug;16(8):975-85. doi: 10.15252/embr.201439951. Epub 2015 Jun 26.

Authors

Xian-Bo Lv¹, Chen-Ying Liu², Zhen Wang¹, Yi-Ping Sun¹, Yue Xiong³, Qun-Ying Lei⁴, Kun-Liang Guan⁵

Affiliations

¹ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology Fudan University Shanghai Medical College, Shanghai, China Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China School of Life Science, Fudan University, Shanghai, China.
² Department of Colorectal and Anal Surgery, Shanghai Colorectal Cancer Research Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
³ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology Fudan University Shanghai Medical College, Shanghai, China Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA yxiong@mai.unc.edu qlei@fudan.edu.cn kuguan@ucsd.edu.
⁴ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology Fudan University Shanghai Medical College, Shanghai, China Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China yxiong@mai.unc.edu qlei@fudan.edu.cn kuguan@ucsd.edu.
⁵ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology Fudan University Shanghai Medical College, Shanghai, China Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA yxiong@mai.unc.edu qlei@fudan.edu.cn kuguan@ucsd.edu.

Abstract

The Hippo pathway plays a major role in organ size control, and its dysregulation contributes to tumorigenesis. The major downstream effectors of the Hippo pathway are the YAP/TAZ transcription co-activators, which are phosphorylated and inhibited by the Hippo pathway kinase LATS1/2. Here, we report a novel mechanism of TAZ regulation by the tight junction protein PARD3. PARD3 promotes the interaction between PP1A and LATS1 to induce LATS1 dephosphorylation and inactivation, therefore leading to dephosphorylation and activation of TAZ. The cytoplasmic, but not the tight junction complex associated, PARD3 is responsible for TAZ regulation. Our study indicates a potential molecular basis for cell growth-promoting function of PARD3 by modulating the Hippo pathway signaling in response to cell contact and cell polarity signals.

Keywords: Hippo pathway; PARD3; TAZ; tight junction.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Line, Tumor
Cell Polarity
Cell Proliferation*
Gene Expression Regulation
HEK293 Cells
Hippo Signaling Pathway
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Phosphoprotein Phosphatases / metabolism*
Phosphorylation
Protein Serine-Threonine Kinases / genetics*
Signal Transduction
Tight Junction Proteins / genetics
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Intracellular Signaling Peptides and Proteins
Membrane Proteins
PARD3 protein, human
Tight Junction Proteins
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
WWTR1 protein, human
LATS1 protein, human
Protein Serine-Threonine Kinases
Phosphoprotein Phosphatases