title: PARD3 induces TAZ activation and cell growth by promoting LATS1 and PP1 interaction.
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.
authors.affiliation: 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.
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Lv
authors.affiliation: Department of Colorectal and Anal Surgery, Shanghai Colorectal Cancer Research Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chen-Ying
authors.initials: CY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Lei
authors.affiliation: 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.
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016764:Cell Polarity; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction; D062725:Tight Junction Proteins / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human; D062725:Tight Junction Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases
keywords: Hippo pathway; PARD3; TAZ; tight junction