Cited by 386Hippo pathway signaling and YAP/TAZMicrotubule and mitosis dynamicsSignaling Pathways in Disease

Hippo Pathway-independent Restriction of TAZ and YAP by Angiomotin

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Chan, Siew Wee, Lim, Chun Jye, Chong, Yaan Fun, Pobbati, Ajaybabu V., Huang, Caixia, Hong, Wanjin·2011·Journal of Biological Chemistry

Abstract

The Hippo pathway restricts the activity of transcriptional co-activators TAZ and YAP by phosphorylating them for cytoplasmic sequestration or degradation. In this report, we describe an independent mechanism for the cell to restrict the activity of TAZ and YAP through interaction with angiomotin (Amot) and angiomotin-like 1 (AmotL1). Amot and AmotL1 were robustly co-immunoprecipitated with FLAG-tagged TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N terminus of Amot. Amot and AmotL1 also interact with YAP via the first WW domain of YAP. Overexpression of Amot and AmotL1 caused cytoplasmic retention of TAZ and suppressed its transcriptional outcome such as the expression of CTGF and Cyr61. Hippo refractory TAZ mutant (S89A) is also negatively regulated by Amot and AmotL1. HEK293 cells express the highest level of Amot and AmotL1 among nine cell lines examined, and silencing the expression of endogenous Amot increased the expression of CTGF and Cyr61 either at basal levels or upon overexpression of exogenous S89A. These results reveal a novel mechanism to restrict the activity of TAZ and YAP through physical interaction with Amot and AmotL1.

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  • CCN1 is a target of TAZ and YAP transcriptional co-activators, which act with transcription factors such as TEAD to regulate proliferation- and apoptosis-related genes.

    “Recent genomic studies have also shown that CCN1 is a target of the TAZ and YAP transcriptional co-activators, which act in concert with various transcription factors such as TEAD to regulate expression of genes related to proliferation and apoptosis [45,46].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [45]

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References 39 · Cited by 386

Authors
Chan, S. W., Lim, C. J., Chong, Y. F., Pobbati, A. V., Huang, C., & Hong, W.
Affiliations
  • Institute of Molecular and Cell Biology (SG)
  • National University of Singapore (SG)
Corresponding author
Hong, Wanjin
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2011-03
Volume
286
Issue
9
Pages
7018-7026
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2108260772
Cited by
386
References
39
Citations by year
2026: 6 · 2025: 16 · 2024: 26 · 2023: 12 · 2022: 16 · 2021: 22 · 2020: 26 · 2019: 25 · 2018: 32 · 2017: 23 · 2016: 30 · 2015: 33 · 2014: 33 · 2013: 42 · 2012: 27
FWCI
18.11
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
angiomotin, TAZ, YAP, Hippo signaling pathway, WW domain, PPxY motif, protein-protein interaction, cytoplasmic retention, transcriptional coactivator, connective tissue growth factor, CYR61
MeSH terms
Angiomotins, YAP-Signaling Proteins, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Cell Division, Cytoplasm, Humans, Membrane Proteins, Microfilament Proteins, Phosphoproteins, Transcription Factors, Transcription, Genetic, Signal Transduction, Trans-Activators, Protein Structure, Tertiary, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Protein Interaction Domains and Motifs, Connective Tissue Growth Factor, HEK293 Cells

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