Abstract
The Yes-associated protein (YAP) is a transcriptional factor involved in tissue development and tumorigenesis. Although YAP has been recognized as a key element of the Hippo signaling pathway, the mechanisms that regulate YAP activities remain to be fully characterized. In this study, we demonstrate that the non-receptor type protein tyrosine phosphatase 14 (PTPN14) functions as a negative regulator of YAP. We show that YAP forms a protein complex with PTPN14 through the WW domains of YAP and the PPXY motifs of PTPN14. In addition, PTPN14 inhibits YAP-mediated transcriptional activities. Knockdown of YAP sensitizes cancer cells to various anti-cancer agents, such as cisplatin, the EGFR tyrosine kinase inhibitor erlotinib and the small-molecule antagonist of survivin, S12. YAP-targeted modalities may be used in combination with other cancer drugs to achieve maximal therapeutic effects.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acyltransferases
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Motifs
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Animals
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Cisplatin / pharmacology
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Erlotinib Hydrochloride
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Gene Knockdown Techniques
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Genes, Reporter
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HEK293 Cells
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Humans
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Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
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Inhibitor of Apoptosis Proteins / metabolism
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Luciferases, Renilla / biosynthesis
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Luciferases, Renilla / genetics
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Mice
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NIH 3T3 Cells
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Peptide Fragments / chemistry
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Binding
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Protein Interaction Domains and Motifs
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Protein Interaction Mapping
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Protein Tyrosine Phosphatases, Non-Receptor / chemistry
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Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
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Quinazolines / pharmacology*
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RNA, Small Interfering / genetics
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Survivin
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Transcription Factors / metabolism
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Transcriptional Activation
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Antineoplastic Agents
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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Peptide Fragments
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Phosphoproteins
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Quinazolines
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RNA, Small Interfering
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Survivin
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Transcription Factors
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YAP-Signaling Proteins
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YAP1 protein, human
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Erlotinib Hydrochloride
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Luciferases, Renilla
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Acyltransferases
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TAFAZZIN protein, human
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ErbB Receptors
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PTPN14 protein, human
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Protein Tyrosine Phosphatases, Non-Receptor
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Cisplatin