title: Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein.
abstract: The Yes-associated protein (YAP) is a transcription coactivator that plays a crucial role in organ size control by promoting cell proliferation and inhibiting apoptosis. The Hippo tumor suppressor pathway inhibits YAP through phosphorylation-induced cytoplasmic retention and degradation. Here we report a novel mechanism of YAP regulation by angiomotin (AMOT) family proteins via a direct interaction. Knockdown of AMOT family protein AMOTL2 in polarized Madin-Darby canine kidney (MDCK) cells leads to YAP activation, as indicated by decreased YAP tight junction localization, attenuated YAP phosphorylation, accumulation of nuclear YAP, and induction of YAP target gene expression. Transcriptional coactivator with PDZ-binding motif (TAZ), the YAP paralog, is also regulated by AMOT in a similar fashion. Furthermore, AMOTL2 knockdown results in loss of cell contact inhibition in a manner dependent on the functions of YAP and TAZ. Our results indicate a potential tumor-suppressing role of AMOT family proteins as components of the Hippo pathway, and demonstrate a novel mechanism of YAP and TAZ inhibition by AMOT-mediated tight junction localization. These observations provide a potential link between the Hippo pathway and cell contact inhibition.
authors.affiliation: Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Lloyd H
authors.initials: LH
authors.lastname: Wang
authors.forename: Chen-Ying
authors.initials: CY
authors.lastname: Liu
authors.forename: Qunying
authors.initials: Q
authors.lastname: Lei
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D000091082:Angiomotins; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C423985:AMOT protein, human; D000091082:Angiomotins; D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D017346:Protein Serine-Threonine Kinases