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Title 

Hippo signaling is intrinsically regulated during cell cycle progression by APC/CCdh1

Authors 

Wantae KimY S ChoX WangO ParkX MaH KimW GanE H JhoB ChaYun-Ji JeungL ZhangB GaoW WeiJ JiangKyung-Sook ChungY Yang

Publisher 

National Academy of Sciences

Issue Date 

2019

Citation 

Proceedings of the National Academy of Sciences of the United States of America

Abstract 

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecularmechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/CCdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

URI 

https://doi.org/10.1073/pnas.1821370116/-/DCSupplemental

ISSN 

0027-8424

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-07-10


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