Michaloglou, C. and Lehmann, W. and Martin, T. and Delaunay, C. and Hueber, A. and Barys, L. and Niu, H. and Billy, E. and Wartmann, M. and Ito, M. and Wilson, C. J. and Digan, M. E. and Bauer, A. and Voshol, H. and Christofori, G. and Sellers, W. R. and Hofmann, F. and Schmelzle, T.. (2013) The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity. PLoS one, Vol. 8, H. 4 , e61916.
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Official URL: http://edoc.unibas.ch/dok/A6338674
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Abstract
The Hippo (Hpo) pathway is a novel signaling pathway that controls organ size in Drosophila and mammals and is deregulated in a variety of human cancers. It consists of a set of kinases that, through a number of phosphorylation events, inactivate YAP, a transcriptional co-activator that controls cellular proliferation and apoptosis. We have identified PTPN14 as a YAP-binding protein that negatively regulates YAP activity by controlling its localization. Mechanistically, we find that the interaction of ectopic YAP with PTPN14 can be mediated by the respective WW and PPxY motifs. However, the PTPN14 PPxY motif and phosphatase activity appear to be dispensable for the negative regulation of endogenous YAP, likely suggesting more complex mechanisms of interaction and modulation. Finally, we demonstrate that PTPN14 downregulation can phenocopy YAP activation in mammary epithelial cells and synergize with YAP to induce oncogenic transformation.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Tumor Biology (Christofori) |
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UniBasel Contributors: | Christofori, Gerhard M. |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Public Library of Science |
ISSN: | 1932-6203 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
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Identification Number: |
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Last Modified: | 10 Apr 2015 09:13 |
Deposited On: | 10 Apr 2015 09:13 |
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