title: YAP1 recruits c-Abl to protect angiomotin-like 1 from Nedd4-mediated degradation.
abstract: BACKGROUND
  Tissue development and organ growth require constant remodeling of cell-cell contacts formed between epithelial cells. The Hippo signaling cascade curtails organ growth by excluding the transcriptional co-activator Yes Associated Protein 1 (YAP1) from the nucleus. Angiomotin family members recruit YAP1 to tight junctions [1], but whether YAP1 plays a specific role outside of the nucleus is currently unknown.
  
  
  RESULTS
  The present study demonstrates that the E3 ubiquitin ligase Nedd4.2 targets Angiomotin-like 1 (AMOTL1), a family member that promotes the formation of epithelial tight junctions, for ubiquitin-dependent degradation. Unexpectedly, YAP1 antagonizes the function of Nedd4.2, and protects AMOTL1 against Nedd4.2-mediated degradation. YAP1 recruits c-Abl, a tyrosine kinase that binds and phosphorylates Nedd4.2 on tyrosine residues, thereby modifying its ubiquitin-ligase activity.
  
  
  CONCLUSIONS
  Our results uncover a novel function for cytoplasmic YAP1. YAP1 recruits c-Abl to protect AMOTL1 against Nedd4.2-mediated degradation. Thus, YAP1, excluded from the nucleus, contributes to the maintenance of tight junctions.
authors.affiliation: Renal Division, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Kassiani
authors.initials: K
authors.lastname: Skouloudaki
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000091082:Angiomotins; D000818:Animals; D002460:Cell Line; D004285:Dogs; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D000075702:Nedd4 Ubiquitin Protein Ligases; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D019108:Tight Junctions / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000091102:YAP-Signaling Proteins
chemical_list: C510063:AMOTL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000091082:Angiomotins; D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D025801:Ubiquitin; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases; D016315:Proto-Oncogene Proteins c-abl; D046988:Proteasome Endopeptidase Complex