YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity
Open accessAbstract
The Hippo TEAD-transcriptional regulators YAP1 and TAZ are central for cell renewal and cancer growth; however, the specific downstream gene networks involved in their activity are not completely understood. Here we introduce TEADi, a genetically encoded inhibitor of the interaction of YAP1 and TAZ with TEAD, as a tool to characterize the transcriptional networks and biological effects regulated by TEAD transcription factors. Blockage of TEAD activity by TEADi in human keratinocytes and mouse skin leads to reduced proliferation and rapid activation of differentiation programs. Analysis of gene networks affected by TEADi and YAP1/TAZ knockdown identifies KLF4 as a central transcriptional node regulated by YAP1/TAZ-TEAD in keratinocyte differentiation. Moreover, we show that TEAD and KLF4 can regulate the activity of each other, indicating that these factors are part of a transcriptional regulatory loop. Our study establishes TEADi as a resource for studying YAP1/TAZ-TEAD dependent effects.
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Expression of a dominant negative TEAD1 mutant had similar enhancing effects.
“Expressing a dominant negative TEAD1 mutant (37) had similar effects”
From Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy (2023) · cites this paper as [37]
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- Authors
- Yuan, Y., Park, J., Feng, A., Awasthi, P., Wang, Z., Chen, Q., & Iglesias-Bartolome, R.
- Affiliations
- National Institutes of Health (US)
- Sichuan University (CN)
- ORCID
- Venue
- Nature Communications
- Published
- 2020-03-19
- Volume
- 11
- Issue
- 1
- Pages
- 1472-1472
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7081327
- OpenAlex
- W3011179253
- Cited by
- 137
- References
- 50
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 25 · 2023: 20 · 2022: 23 · 2021: 14 · 2020: 5
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (ZIA BC 011764, ZIA BC 011763)
- 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 › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- YAP, TAZ, TEAD transcription factors, Hippo signaling pathway, keratinocytes, skin homeostasis, cell proliferation, keratinocyte differentiation, KLF4, transcriptional regulatory networks
- MeSH terms
- Kruppel-Like Factor 4, YAP-Signaling Proteins, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Animals, Binding Sites, Cell Differentiation, Homeostasis, Humans, Inflammation, Models, Biological, Protein Binding, Skin, Stem Cells, Transcription Factors, Transcription, Genetic, Trans-Activators, Keratinocytes, Cell Cycle Proteins, Models, Animal, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, Kruppel-Like Transcription Factors, Gene Regulatory Networks, HEK293 Cells, Cell Cycle Checkpoints
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