Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex

Abstract The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and...

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Autores principales:	Hung Yi Kristal Kaan, Siew Wee Chan, Siew Kim Joyce Tan, Fusheng Guo, Chun Jye Lim, Wanjin Hong, Haiwei Song
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bf830a5d4964108b7004c7392d27c69
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spelling	oai:doaj.org-article:8bf830a5d4964108b7004c7392d27c692021-12-02T11:41:00ZCrystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex10.1038/s41598-017-02219-92045-2322https://doaj.org/article/8bf830a5d4964108b7004c7392d27c692017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02219-9https://doaj.org/toc/2045-2322Abstract The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure. The second is a unique binding mode, whereby two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the latter using cross-linking and multi-angle light scattering. Using siRNA, we showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly, results from luciferase assays, using YAP/TAZ transfected or knockdown cells, give support to the non-redundancy of YAP/TAZ co-activators in regulating gene expression in the Hippo pathway.Hung Yi Kristal KaanSiew Wee ChanSiew Kim Joyce TanFusheng GuoChun Jye LimWanjin HongHaiwei SongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hung Yi Kristal Kaan Siew Wee Chan Siew Kim Joyce Tan Fusheng Guo Chun Jye Lim Wanjin Hong Haiwei Song Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex
description	Abstract The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure. The second is a unique binding mode, whereby two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the latter using cross-linking and multi-angle light scattering. Using siRNA, we showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly, results from luciferase assays, using YAP/TAZ transfected or knockdown cells, give support to the non-redundancy of YAP/TAZ co-activators in regulating gene expression in the Hippo pathway.
format	article
author	Hung Yi Kristal Kaan Siew Wee Chan Siew Kim Joyce Tan Fusheng Guo Chun Jye Lim Wanjin Hong Haiwei Song
author_facet	Hung Yi Kristal Kaan Siew Wee Chan Siew Kim Joyce Tan Fusheng Guo Chun Jye Lim Wanjin Hong Haiwei Song
author_sort	Hung Yi Kristal Kaan
title	Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex
title_short	Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex
title_full	Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex
title_fullStr	Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex
title_full_unstemmed	Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex
title_sort	crystal structure of taz-tead complex reveals a distinct interaction mode from that of yap-tead complex
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8bf830a5d4964108b7004c7392d27c69
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Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex

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