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Transcriptional Co-repressor Function of the Hippo Pathway Transducers YAP and TAZ
Open accessAbstract
YAP (yes-associated protein) and TAZ are oncogenic transcriptional co-activators downstream of the Hippo tumor-suppressor pathway. However, whether YAP and/or TAZ (YAP/TAZ) engage in transcriptional co-repression remains relatively unexplored. Here, we directly demonstrated that YAP/TAZ represses numerous target genes, including tumor-suppressor genes such as DDIT4 (DNA-damage-inducible transcript 4) and Trail (TNF-related apoptosis-inducing ligand). Mechanistically, the repressor function of YAP/TAZ requires TEAD (TEA domain) transcription factors. A YAP/TAZ-TEAD complex recruits the NuRD complex to deacetylate histones and alters nucleosome occupancy at target genes. Functionally, repression of DDIT4 and Trail by YAP/TAZ is required for mTORC1 (mechanistic target of rapamycin complex 1) activation and cell survival, respectively. Our demonstration of the transcriptional co-repressor activity of YAP/TAZ opens a new avenue for understanding the Hippo signaling pathway.
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Metadata
- Authors
- Kim, M., Kim, T., Johnson, R. L., & Lim, D.-S.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 11
- Issue
- 2
- Pages
- 270-282
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2087766778
- Cited by
- 287
- References
- 42
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- gold
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