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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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162497
Files in This Item:
T201801771.pdf Download
DOI
10.1038/s41467-018-04757-w
Appears in Collections:
3. YUHS Publication (연세의료원 간행물) > 2. College of Dentistry (치과대학) > Dept. of Preventive Dentistry (예방치과학교실) > 10th Anniversary of Department of preventive Dentistry & public oral health College of dentistry Yonsei University
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소)
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실)
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실)
Yonsei Authors
강치구(Kang, Chi Gu)
김남희(Kim, Nam Hee) ORCID logo https://orcid.org/0000-0002-3087-5276
김현실(Kim, Hyun Sil) ORCID logo https://orcid.org/0000-0003-3614-1764
양지혜(Yang, Ji Hye)
육종인(Yook, Jong In) ORCID logo https://orcid.org/0000-0002-7318-6112
차소영(Cha, So Young)
차용훈(Cha, Yong Hoon)
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