Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD
TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing...
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doaj-bd70a4e9206a4019ba44712c116f4c9f2021-05-05T13:25:18ZengeLife Sciences Publications LtdeLife2050-084X2017-04-01610.7554/eLife.25068Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEADYannick Mesrouze0Fedir Bokhovchuk1Marco Meyerhofer2Patrizia Fontana3Catherine Zimmermann4Typhaine Martin5Clara Delaunay6Dirk Erdmann7Tobias Schmelzle8Patrick Chène9https://orcid.org/0000-0002-6010-9169Disease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandDisease Area Oncology, Novartis Institutes for Biomedical Research, Basel, SwitzerlandTEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation. In this report, combining single site-directed mutagenesis and double mutant analyses, we conduct a detailed analysis on the role of several residues located at the YAP:TEAD interface. Our results provide quantitative understanding of the interactions taking place at the YAP:TEAD interface and give insights into the formation of the YAP:TEAD complex and more particularly on the interaction between TEAD and the Ω-loop found in YAP.https://elifesciences.org/articles/25068protein-protein interactionintrinsically disordered proteinmolecular recognitiom |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yannick Mesrouze Fedir Bokhovchuk Marco Meyerhofer Patrizia Fontana Catherine Zimmermann Typhaine Martin Clara Delaunay Dirk Erdmann Tobias Schmelzle Patrick Chène |
spellingShingle |
Yannick Mesrouze Fedir Bokhovchuk Marco Meyerhofer Patrizia Fontana Catherine Zimmermann Typhaine Martin Clara Delaunay Dirk Erdmann Tobias Schmelzle Patrick Chène Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD eLife protein-protein interaction intrinsically disordered protein molecular recognitiom |
author_facet |
Yannick Mesrouze Fedir Bokhovchuk Marco Meyerhofer Patrizia Fontana Catherine Zimmermann Typhaine Martin Clara Delaunay Dirk Erdmann Tobias Schmelzle Patrick Chène |
author_sort |
Yannick Mesrouze |
title |
Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD |
title_short |
Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD |
title_full |
Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD |
title_fullStr |
Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD |
title_full_unstemmed |
Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD |
title_sort |
dissection of the interaction between the intrinsically disordered yap protein and the transcription factor tead |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-04-01 |
description |
TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation. In this report, combining single site-directed mutagenesis and double mutant analyses, we conduct a detailed analysis on the role of several residues located at the YAP:TEAD interface. Our results provide quantitative understanding of the interactions taking place at the YAP:TEAD interface and give insights into the formation of the YAP:TEAD complex and more particularly on the interaction between TEAD and the Ω-loop found in YAP. |
topic |
protein-protein interaction intrinsically disordered protein molecular recognitiom |
url |
https://elifesciences.org/articles/25068 |
work_keys_str_mv |
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