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Structural basis of YAP recognition by TEAD4 in the hippo pathway

DOI: 10.1101/gad.1865310 DOI Help

Authors: Liming Chen (Institute of Molecular and Cell Biology) , Siew Wee Chan (Institute of Molecular and Cell Biology) , Xiaoqian Zhang (Institute of Molecular and Cell Biology) , Martin Walsh (Diamond Light Source) , Chun Jye Lim (Institute of Molecular and Cell Biology) , Wanjin Hong (Institute of Molecular and Cell Biology; National University of Singapore) , Haiwei Song (of Molecular and Cell Biology; National University of Singapore)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Genes And Development , VOL 24 , PAGES 290-300

State: Published (Approved)
Published: February 2010

Abstract: The Hippo signaling pathway controls cell growth, proliferation, and apoptosis by regulating the expression of target genes that execute these processes. Acting downstream from this pathway is the YAP transcriptional coactivator, whose biological function is mediated by the conserved TEAD family transcription factors. The interaction of YAP with TEADs is critical to regulate Hippo pathway-responsive genes. Here, we describe the crystal structure of the YAP-interacting C-terminal domain of TEAD4 in complex with the TEAD-interacting N-terminal domain of YAP. The structure reveals that the N-terminal region of YAP is folded into two short helices with an extended loop containing the PXX?P motif in between, while the C-terminal domain of TEAD4 has an immunoglobulin-like fold. YAP interacts with TEAD4 mainly through the two short helices. Point mutations of TEAD4 indicate that the residues important for YAP interaction are required for its transforming activity. Mutagenesis reveals that the PXX?P motif of YAP, although making few contacts with TEAD4, is important for TEAD4 interaction as well as for the transforming activity.

Journal Keywords: Cell Growth; Proliferation; Apoptosis; Hippo Pathway

Subject Areas: Biology and Bio-materials, Medicine, Chemistry

Facility: ESRF

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