PTPN14 is required for the density-dependent control of YAP1

Genes Dev. 2012 Sep 1;26(17):1959-71. doi: 10.1101/gad.192955.112.

Abstract

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 CRL2(LRR1) (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinar Cells / cytology
  • Acinar Cells / metabolism
  • Acinar Cells / pathology
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Motifs
  • Cell Count
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cytoplasm / metabolism
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein Transport
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • Receptors, Cytokine / metabolism
  • Transcription Factors
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CRLF2 protein, human
  • Phosphoproteins
  • Receptors, Cytokine
  • Transcription Factors
  • YAP1 (Yes-associated) protein, human
  • Ubiquitin-Protein Ligases
  • PTPN14 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor