Dissection of the Interaction Between the Intrinsically Disordered YAP Protein and the Transcription Factor TEAD

Overview

Journal Elife

Specialty Biology

Date 2017 Apr 22

PMID 28430104

Citations 28

Authors

Yannick Mesrouze

Fedir Bokhovchuk

Marco Meyerhofer

Patrizia Fontana

Catherine Zimmermann

Typhaine Martin

Clara Delaunay

Dirk Erdmann

Tobias Schmelzle

Patrick Chene

Affiliations

Soon will be listed here.

Abstract

TEAD (/ATTS omain) transcription factors are the most distal effectors of the Hippo pathway. YAP (es-ssociated rotein) 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.

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