Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ

Minchul Kim; Taekhoon Kim; Randy L. Johnson; Dae Sik Lim

doi:10.1016/j.celrep.2015.03.015

Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ

Minchul Kim, Taekhoon Kim, Randy L. Johnson, Dae Sik Lim

Cancer Biology

Research output: Contribution to journal › Article › peer-review

209 Scopus citations

Abstract

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 corepressor activity of YAP/TAZ opens a new avenue for understanding the Hippo signaling pathway.

Original language	English (US)
Pages (from-to)	270-282
Number of pages	13
Journal	Cell Reports
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2015.03.015
State	Published - 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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@article{31884e7238dc4228bded68e46269b095,

title = "Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ",

abstract = "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 corepressor activity of YAP/TAZ opens a new avenue for understanding the Hippo signaling pathway.",

author = "Minchul Kim and Taekhoon Kim and Johnson, {Randy L.} and Lim, {Dae Sik}",

note = "Funding Information: We thank Dr. Mi-ok Lee (SNU) for MTA1 and shMTA1 constructs and Dr. Jeffrey Wrana (Mount Sinai Hospital) for MTA2/3 constructs. This work was funded by the National Institutes of Health Grants HD060579 (to R.L.J.) and the National Creative Research Program (20120001228, to D.-S.L.). ",

year = "2015",

doi = "10.1016/j.celrep.2015.03.015",

language = "English (US)",

volume = "11",

pages = "270--282",

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AU - Kim, Minchul

AU - Kim, Taekhoon

AU - Johnson, Randy L.

AU - Lim, Dae Sik

N1 - Funding Information: We thank Dr. Mi-ok Lee (SNU) for MTA1 and shMTA1 constructs and Dr. Jeffrey Wrana (Mount Sinai Hospital) for MTA2/3 constructs. This work was funded by the National Institutes of Health Grants HD060579 (to R.L.J.) and the National Creative Research Program (20120001228, to D.-S.L.).

PY - 2015

Y1 - 2015

N2 - 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 corepressor activity of YAP/TAZ opens a new avenue for understanding the Hippo signaling pathway.

AB - 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 corepressor activity of YAP/TAZ opens a new avenue for understanding the Hippo signaling pathway.

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Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ

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