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

M Kim, T Kim, RL Johnson, DS Lim - Cell reports, 2015 - cell.com
Cell reports, 2015cell.com
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 …
Summary
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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