@article {1503160,
	title = {Hippo signaling is intrinsically regulated during cell cycle progression by APC/C},
	journal = {Proc Natl Acad Sci U S A},
	volume = {116},
	number = {19},
	year = {2019},
	month = {2019 05 07},
	pages = {9423-9432},
	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) 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  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/C represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.},
	keywords = {Anaphase-Promoting Complex-Cyclosome, Animals, Antigens, CD, Cadherins, Cdh1 Proteins, Drosophila melanogaster, Drosophila Proteins, G1 Phase, HEK293 Cells, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Signal Transduction},
	issn = {1091-6490},
	doi = {10.1073/pnas.1821370116},
	author = {Kim, Wantae and Cho, Yong Suk and Wang, Xiaohui and Park, Ogyi and Ma, Xueyan and Kim, Hanjun and Gan, Wenjian and Jho, Eek-Hoon and Cha, Boksik and Jeung, Yun-Ji and Zhang, Lei and Gao, Bin and Wei, Wenyi and Jiang, Jin and Chung, Kyung-Sook and Yang, Yingzi}
}
