Document Detail


The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals.
MedLine Citation:
PMID:  20643348     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The conserved Hippo signaling pathway regulates organ size in 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 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 phenotypes in multiple tissues were 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.
Authors:
Nailing Zhang; Haibo Bai; Karen K David; Jixin Dong; Yonggang Zheng; Jing Cai; Marco Giovannini; Pentao Liu; Robert A Anders; Duojia Pan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Developmental cell     Volume:  19     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-08-30     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27-38     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / deficiency,  genetics,  physiology*
Animals
Base Sequence
Bile Ducts / growth & development
Cell Survival / physiology
DNA Primers / genetics
Hepatocytes / cytology,  physiology
Heterozygote
Homeostasis / genetics,  physiology
Liver / growth & development,  physiopathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Neurofibromin 2 / deficiency,  genetics,  physiology*
Organ Size
Phenotype
Phosphoproteins / deficiency,  genetics,  physiology*
Signal Transduction
Grant Support
ID/Acronym/Agency:
R01 DK081417/DK/NIDDK NIH HHS; R01 DK081417-04/DK/NIDDK NIH HHS; R01 DK081417-05/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/DNA Primers; 0/Neurofibromin 2; 0/Phosphoproteins; 0/Yap protein, mouse
Comments/Corrections
Comment In:
Dev Cell. 2010 Sep 14;19(3):363-4   [PMID:  20833359 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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