title: YAP-mediated induction of monoacylglycerol lipase restrains oncogenic transformation.
abstract: The Hippo pathway is an evolutionarily conserved regulator of normal and oncogenic growth. Engagement of Hippo pathway signaling results in the inactivation of the transcriptional coactivator YAP by preventing its nuclear entry. The mechanisms underlying the oncogenic properties of YAP remain incompletely understood. Here we find that although the transactivation (TA) domain of YAP mediates YAP-dependent gene expression, it serves as an inhibitor of YAP-mediated anchorage-independent growth. We identify monoacylglycerol lipase (MAGL) as a YAP transcriptional target and an inhibitor of anchorage-dependent cell growth. Significantly, knockdown of MAGL expression leads to the augmentation of YAP-dependent cell transformation. Our results identify MAGL as a transcriptional target of YAP that restrains YAP-mediated cellular transformation.
authors: Laboratory of Molecular Signaling, Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, United States. Electronic address: edtang@ucla.edu.
authors: Eric D
authors: ED
authors: Tang
authors: Laboratory of Molecular Signaling, Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, United States. Electronic address: cwang@dentistry.ucla.edu.
authors: Cun-Yu
authors: CY
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008994:Monoacylglycerol Lipases / Q000235:genetics*; D010750:Phosphoproteins / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D008994:Monoacylglycerol Lipases
keywords: Cancer; Cell transformation; Transcriptional activation; YAP
references: Genes Dev. 2010 May;24(9):862-74
references: 20439427
references: Chem Phys Lipids. 2002 Dec 31;121(1-2):149-58
references: 12505697
references: EMBO J. 1999 May 4;18(9):2551-62
references: 10228168
references: Genes Dev. 2008 Jul 15;22(14):1962-71
references: 18579750
references: Genes Cells. 2009 May;14(5):607-15
references: 19371381
references: Genes Dev. 2010 Jan 1;24(1):72-85
references: 20048001
references: Genes Dev. 2013 Feb 15;27(4):355-71
references: 23431053
references: J Biol Chem. 2002 Dec 20;277(51):50137-42
references: 12393863
references: Dev Cell. 2010 Oct 19;19(4):491-505
references: 20951342
references: Development. 2011 Jan;138(1):9-22
references: 21138973
references: Dev Dyn. 2012 Jan;241(1):3-15
references: 22174083
references: PLoS One. 2012;7(2):e31994
references: 22359650
references: Oncogene. 2013 Jan 10;32(2):234-41
references: 22349814
references: Cell. 2010 Jan 8;140(1):49-61
references: 20079333