NDLI: The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals

Content Provider	PubMed Central
Author	Zhang, Nailing Bai, Haibo David, Karen K. Dong, Jixin Zheng, Yonggang Cai, Jing Giovannini, Marco Liu, Pentao Anders, Robert A. Pan, Duojia
Copyright Year	2010
Abstract	The conserved Hippo signaling pathway regulates organ size in both Drosophila and mammals. While a core kinase cascade leading from the protein kinase Hippo (Hpo) (Mst1 and Mst2 in mammals) to the transcription coactivator Yorkie (Yki) (YAP in mammals) has been established, upstream regulators of the Hippo kinase cascade are less well defined, especially in mammals. Using liver-specific conditional knockout mice, we demonstrate that the Merlin/NF2 tumor suppressor and the YAP oncoprotein function antagonistically to regulate liver development. While inactivation of Yap led to loss of hepatocytes and biliary epithelial cells, inactivation of Nf2 led to hepatocellular carcinoma and bile duct hamartoma. Strikingly, the Nf2-deficient phenotype was largely suppressed by heterozygous deletion of Yap, suggesting that YAP is a major effector of Merlin/NF2 in growth regulation. Our studies link Merlin/NF2 to mammalian Hippo signaling and implicate YAP activation as a mediator of pathologies relevant to Neurofibromatosis 2.
Related Links	http://dx.doi.org/10.1016/j.devcel.2010.06.015
Ending Page	38
Page Count	12
Starting Page	27
File Format	PDF
ISSN	15345807
e-ISSN	18781551
Journal	Developmental cell
Issue Number	1
Volume Number	19
Language	English
Publisher Date	2010-07-01
Access Restriction	Open
Subject Keyword	Developmental Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Molecular Biology

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