Bibliographic Details
| Title: |
Hippo signaling is intrinsically regulated during cell cycle progression by APC/CCdh1. |
| Authors: |
Wantae Kim1,2,3, Yong Suk Cho4, Xiaohui Wang1, Ogyi Park5, Xueyan Ma6, Hanjun Kim1, Wenjian Gan7, Eek-hoon Jho8, Boksik Cha9, Yun-ji Jeung2, Lei Zhang6, Bin Gao5, Wenyi Wei7, Jin Jiang4, Kyung-Sook Chung2 kschung@kribb.re.kr, Yingzi Yanga1 yingzi_yang@hsdm.harvard.edu |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America. 5/7/2019, Vol. 116 Issue 19, p9423-9432. 10p. |
| Subject Terms: |
*CELL cycle, *CELL proliferation, *GENE expression, *APOPTOSIS, *MESSENGER RNA |
| 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 molecular mechanisms 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
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