PTPN14 is required for the density-dependent control of YAP1
PTPN14 is required for the density-dependent control of YAP1
Through an shRNA-mediated loss-of-function screen, we identified PTPN14 as a potential tumor suppressor. PTPN14 interacts with yes-associated protein 1 (YAP1), a member of the hippo signaling pathway. We showed that PTPN14 promotes the nucleus-to-cytoplasm translocation of YAP1 during contact inhibition and thus inhibits YAP1 transactivation activity. Interestingly, PTPN14 protein stability was positively controlled by cell density. We identified the CRL2LRR1(cullin2 RING ubiquitin ligase complex/leucine-rich repeat protein 1) complex as the E3 ligase that targets PTPN14 for degradation at low cell density. Collectively, these data suggest that PTPN14 acts to suppress cell proliferation by promoting cell density-dependent cytoplasmic translocation of YAP1.
- The University of Texas MD Anderson Cancer Center United States
- Zhejiang Ocean University China (People's Republic of)
- Life Sciences Institute United States
- The University of Texas System United States
Cell Nucleus, Cytoplasm, Ubiquitin-Protein Ligases, Amino Acid Motifs, Cell Count, Acinar Cells, Phosphoproteins, Protein Tyrosine Phosphatases, Non-Receptor, Cell Line, Protein Structure, Tertiary, Protein Transport, Cell Transformation, Neoplastic, HEK293 Cells, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Phosphorylation, Receptors, Cytokine, Adaptor Proteins, Signal Transducing, Transcription Factors
Cell Nucleus, Cytoplasm, Ubiquitin-Protein Ligases, Amino Acid Motifs, Cell Count, Acinar Cells, Phosphoproteins, Protein Tyrosine Phosphatases, Non-Receptor, Cell Line, Protein Structure, Tertiary, Protein Transport, Cell Transformation, Neoplastic, HEK293 Cells, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Phosphorylation, Receptors, Cytokine, Adaptor Proteins, Signal Transducing, Transcription Factors
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