MRTF Potentiates TEAD-YAP Transcriptional Activity Causing Metastasis

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2016 Dec 29

PMID 28028053

Citations 69

Authors

Tackhoon Kim

Daehee Hwang

Dahye Lee

Jeong-Hwan Kim

Seon-Young Kim

Dae-Sik Lim

Affiliations

Soon will be listed here.

Abstract

Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity. We show this interaction of MRTF and YAP is critical for LPA-induced cancer cell invasion and breast cancer metastasis to the lung We also demonstrate the significance of MRTF-YAP binding in regulation of YAP activity upon acute actin cytoskeletal damage. Acute actin disruption induces nucleo-cytoplasmic shuttling of MRTF, and this process underlies the LATS-independent regulation of YAP activity. Our results provide clear evidence of crosstalk between MRTF and YAP independent of the LATS kinases that normally act upstream of YAP signaling. Our results also suggest a mechanism by which extracellular stimuli can coordinate physiological events downstream of YAP.

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