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Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner

Authors
 Yoonmi Lee  ;  Nam Hee Kim  ;  Eunae Sandra Cho  ;  Ji Hye Yang  ;  Yong Hoon Cha  ;  Hee Eun Kang  ;  Jun Seop Yun  ;  Sue Bean Cho  ;  Seon-Hyeong Lee  ;  Petra Paclikova  ;  Tomasz W Radaszkiewicz  ;  Vitezslav Bryja  ;  Chi Gu Kang  ;  Young Soo Yuk  ;  So Young Cha  ;  Soo-Youl Kim  ;  Hyun Sil Kim  ;  Jong In Yook 
Citation
 Nature Communications, Vol.9(1) : 2301, 2018 
Journal Title
 Nature Communications 
Issue Date
2018
Abstract
Phosphorylation-dependent YAP translocation is a well-known intracellular mechanism of the Hippo pathway; however, the molecular effectors governing YAP cytoplasmic translocation remains undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses Wnt activity. Here, we show that Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated YAP. Mutational inactivation of the nuclear export signal embedded in DVL leads to nuclear YAP retention, with an increase in TEAD transcriptional activity. DVL is also required for YAP subcellular localization induced by E-cadherin, alpha-catenin, or AMPK activation. Importantly, the nuclear-cytoplasmic trafficking is dependent on the p53-Lats2 or LKB1-AMPK tumor suppressor axes, which determine YAP phosphorylation status. In vivo and clinical data support that the loss of p53 or LKB1 relieves DVL-linked reciprocal inhibition between the Wnt and nuclear YAP activity. Our observations provide mechanistic insights into controlled proliferation coupled with epithelial polarity during development and human cancer.
Files in This Item:
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DOI
10.1038/s41467-018-04757-w
Appears in Collections:
2. College of Dentistry (치과대학) > Others (기타) > 4. Publications
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chi Gu(강치구)
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yang, Ji Hye(양지혜)
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Cho, Eunae(조은애산드라) ORCID logo https://orcid.org/0000-0002-0820-3019
Cha, So Young(차소영) ORCID logo https://orcid.org/0000-0002-2810-3883
Cha, Yong Hoon(차용훈) ORCID logo https://orcid.org/0000-0003-1761-3260
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162497
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