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Title 

MRTF potentiates TEAD-YAP transcriptional activity causing metastasis

Authors 

T KimD HwangD LeeJeong Hwan KimSeon-Young KimD S Lim

Publisher 

Nature Publishing Group

Issue Date 

2012

Citation 

EMBO Journal

Keywords 

cytoskeletal damagemetastasisMRTFTEAD-YAP

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 in?vitro and breast cancer metastasis to the lung in?vivo. 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.

ISSN 

0261-4190

Link 

http://dx.doi.org/10.15252/embj.201695137

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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