Cited 33 times in
MAML1/2 promote YAP/TAZ nuclear localization and tumorigenesis
DC Field | Value | Language |
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dc.contributor.author | 정희철 | - |
dc.contributor.author | 김혜련 | - |
dc.date.accessioned | 2021-09-29T02:30:22Z | - |
dc.date.available | 2021-09-29T02:30:22Z | - |
dc.date.issued | 2020-06 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/184944 | - |
dc.description.abstract | The Hippo pathway plays a pivotal role in tissue homeostasis and tumor suppression. YAP and TAZ are downstream effectors of the Hippo pathway, and their activities are tightly suppressed by phosphorylation-dependent cytoplasmic retention. However, the molecular mechanisms governing YAP/TAZ nuclear localization have not been fully elucidated. Here, we report that Mastermind-like 1 and 2 (MAML1/2) are indispensable for YAP/TAZ nuclear localization and transcriptional activities. Ectopic expression or depletion of MAML1/2 induces nuclear translocation or cytoplasmic retention of YAP/TAZ, respectively. Additionally, mutation of the MAML nuclear localization signal, as well as its YAP/TAZ interacting region, both abolish nuclear localization and transcriptional activity of YAP/TAZ. Importantly, we demonstrate that the level of MAML1 messenger RNA (mRNA) is regulated by microRNA-30c (miR-30c) in a cell-density-dependent manner. In vivo and clinical results suggest that MAML potentiates YAP/TAZ oncogenic function and positively correlates with YAP/TAZ activation in human cancer patients, suggesting pathological relevance in the context of cancer development. Overall, our study not only provides mechanistic insight into the regulation of YAP/TAZ subcellular localization, but it also strongly suggests that the miR30c-MAML-YAP/TAZ axis is a potential therapeutic target for developing novel cancer treatments. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | National Academy of Sciences | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing / genetics | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing / metabolism* | - |
dc.subject.MESH | Carcinogenesis / genetics | - |
dc.subject.MESH | Carcinogenesis / metabolism | - |
dc.subject.MESH | Cell Nucleus / genetics | - |
dc.subject.MESH | Cell Nucleus / metabolism* | - |
dc.subject.MESH | DNA-Binding Proteins / genetics | - |
dc.subject.MESH | DNA-Binding Proteins / metabolism* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | MicroRNAs / genetics | - |
dc.subject.MESH | MicroRNAs / metabolism | - |
dc.subject.MESH | Neoplasms / genetics | - |
dc.subject.MESH | Neoplasms / metabolism* | - |
dc.subject.MESH | Protein Transport | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Trans-Activators / genetics | - |
dc.subject.MESH | Trans-Activators / metabolism* | - |
dc.subject.MESH | Transcription Factors / genetics | - |
dc.subject.MESH | Transcription Factors / metabolism* | - |
dc.title | MAML1/2 promote YAP/TAZ nuclear localization and tumorigenesis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Jiyoung Kim | - |
dc.contributor.googleauthor | Hyeryun Kwon | - |
dc.contributor.googleauthor | You Keun Shin | - |
dc.contributor.googleauthor | Gahyeon Song | - |
dc.contributor.googleauthor | Taebok Lee | - |
dc.contributor.googleauthor | Youngeun Kim | - |
dc.contributor.googleauthor | Wonyoung Jeong | - |
dc.contributor.googleauthor | Ukjin Lee | - |
dc.contributor.googleauthor | Xianglan Zhang | - |
dc.contributor.googleauthor | Gilyeong Nam | - |
dc.contributor.googleauthor | Hei-Cheul Jeung | - |
dc.contributor.googleauthor | Wantae Kim | - |
dc.contributor.googleauthor | Eek-Hoon Jho | - |
dc.identifier.doi | 10.1073/pnas.1917969117 | - |
dc.contributor.localId | A03794 | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A06208 | - |
dc.contributor.localId | A04627 | - |
dc.relation.journalcode | J02550 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.pmid | 32482852 | - |
dc.identifier.url | https://www.pnas.org/doi/full/10.1073/pnas.1917969117 | - |
dc.subject.keyword | Hippo signaling | - |
dc.subject.keyword | MAML1/2 | - |
dc.subject.keyword | TEAD | - |
dc.subject.keyword | YAP/TAZ | - |
dc.subject.keyword | nuclear localization | - |
dc.contributor.alternativeName | Jeung, Hei Cheul | - |
dc.contributor.affiliatedAuthor | 정희철 | - |
dc.contributor.affiliatedAuthor | 김혜련 | - |
dc.citation.volume | 117 | - |
dc.citation.number | 24 | - |
dc.citation.startPage | 13529 | - |
dc.citation.endPage | 13540 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.117(24) : 13529-13540, 2020-06 | - |
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