title: PTPN14 interacts with and negatively regulates the oncogenic function of YAP.
abstract: The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. The pivotal effector of this pathway is YAP, a transcriptional co-activator amplified in mouse and human cancers where it promotes epithelial-to-mesenchymal transition and malignant transformation. Here, we report a novel regulatory mechanism for the YAP oncogenic function via direct interaction with non-receptor tyrosine phosphatase 14 (PTPN14) through the WW domain of YAP and the PPxY domain of PTPN14. We also found that YAP is a direct substrate of PTPN14. In addition, luciferase reporter assay showed that the inhibition of the YAP transcriptional co-activator function by PTPN14 is mediated through their protein interactions and may result from an increase in the inactive cytoplasmic form of YAP. Last, knockdown of PTPN14 induces the nuclear retention of YAP and increases the YAP-dependent cell migration. In summary, our results indicate a potential regulatory role of PTPN14 on YAP and demonstrate a novel mechanism in YAP regulation.
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: S A
authors.initials: SA
authors.lastname: Figel
authors.forename: K E
authors.initials: KE
authors.lastname: Wilson
authors.forename: C D
authors.initials: CD
authors.lastname: Morrison
authors.forename: I H
authors.initials: IH
authors.lastname: Gelman
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; C093261:PTPN14 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor