title: Characterization of Hippo Pathway Components by Gene Inactivation.
abstract: The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ. To provide an overview of important Hippo pathway components, we created knockout cell lines for many of these components and compared their relative contributions to YAP/TAZ regulation in response to a wide range of physiological signals. By this approach, we provide an overview of the functional importance of many Hippo pathway components and demonstrate NF2 and RHOA as important regulators of YAP/TAZ and TAOK1/3 as direct kinases for LATS1/2.
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Plouffe
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Lin
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Audrey W
authors.initials: AW
authors.lastname: Hong
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Justin V
authors.initials: JV
authors.lastname: Chun
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: kuguan@ucsd.edu.
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D000217:Acyltransferases; D018797:Cell Cycle Proteins; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D025581:Neurofibromin 2; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025581:Neurofibromin 2; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C456659:YY1AP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; C092745:LATS1 protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases; C115483:TAO1 protein kinase; D020742:rhoA GTP-Binding Protein
keywords: CRISPR; Hippo pathway; NF2; RHOA; TAOK1; TAOK3; TAZ; YAP