title: MRTF potentiates TEAD-YAP transcriptional activity causing metastasis.
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 invasionin vitroand breast cancer metastasis to the lungin vivoWe 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.
authors.affiliation: National Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea tackhoon.k@kaist.ac.kr daesiklim@kaist.ac.kr.
authors.forename: Tackhoon
authors.identifier: 0000-0001-7911-6273
authors.initials: T
authors.lastname: Kim
authors.affiliation: National Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: National Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Dahye
authors.initials: D
authors.lastname: Lee
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Seon-Young
authors.identifier: 0000-0002-1030-7730
authors.initials: SY
authors.lastname: Kim
authors.affiliation: National Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea tackhoon.k@kaist.ac.kr daesiklim@kaist.ac.kr.
authors.forename: Dae-Sik
authors.identifier: 0000-0003-2356-7555
authors.initials: DS
authors.lastname: Lim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism*; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C431575:MRTFA protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3
keywords: MRTF; TEAD‐YAP; cytoskeletal damage; metastasis