Hippo Pathway-independent Restriction of TAZ and YAP by Angiomotin
Open accessAbstract
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)
- PMC
- PMC3044958
- 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
- hybrid
- doi.org
- Licence
- 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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