Transcriptional Co-activator Functions of YAP and TAZ Are Inversely Regulated by Tyrosine Phosphorylation Status of Parafibromin

IScience
Chao TangMasanori Hatakeyama

Abstract

YAP and TAZ, the Hippo signal-regulated transcriptional co-activators, play crucial roles in morphogenesis and organogenesis. Here we report that the YAP/TAZ activities are stimulated upon complex formation with Parafibromin, which undergoes tyrosine phosphorylation and dephosphorylation by kinases such as PTK6 and phosphatases such as SHP2, respectively. Furthermore, TAZ and the Wnt effector β-catenin interact cooperatively with tyrosine-dephosphorylated Parafibromin, which synergistically stimulates the co-activator functions of TAZ and β-catenin. On the other hand, YAP is selectively activated through binding with tyrosine-phosphorylated Parafibromin, which does not interact with β-catenin and thus cannot co-activate YAP and β-catenin. These findings indicate that Parafibromin inversely regulates the activities of YAP and TAZ depending on its tyrosine phosphorylation status. They also suggest that YAP and TAZ exert their redundant and non-redundant biological actions through mutually exclusive interaction with Parafibromin, which is regulated by a balance of kinase and phosphatase activities toward Parafibromin.

Citations

Dec 21, 2018·FEBS Letters·Bernard A CallusSteve D Wilton
Dec 6, 2019·Cellular & Molecular Immunology·Atsushi Takahashi-KanemitsuMasanori Hatakeyama
Aug 25, 2020·Investigative Ophthalmology & Visual Science·Felix YemanyiVijay Krishna Raghunathan
Oct 19, 2019·Journal of Experimental & Clinical Cancer Research : CR·Lei GuanHuqin Zhang
Apr 25, 2020·Cells·Heinrich KovarBranka Radic-Sarikas
Sep 2, 2020·Cancers·Sahar Sarmasti EmamiXiaolong Yang
Nov 21, 2020·Investigative Ophthalmology & Visual Science·Felix Yemanyi, VijayKrishna Raghunathan
Feb 15, 2021·Cellular and Molecular Life Sciences : CMLS·Lucy LeBlancJonghwan Kim
Jul 14, 2021·Reproductive Sciences·Meiyuan JinChao Tang
Apr 24, 2019·Aging and Disease·Qing HeZengqiang Yuan
Aug 16, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Haibin ZhuChao Tang
Aug 31, 2021·Current Opinion in Cell Biology·Guilherme Pedreira de Freitas NaderMatthieu Piel

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Methods Mentioned

BETA
transfection
immunoprecipitation
co-immunoprecipitation
gene knockout

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