title: AMOTL2 interaction with TAZ causes the inhibition of surfactant proteins expression in lung cells.
abstract: BACKGROUND
  TAZ (Transcriptional co-Activator with PDZ-binding motif), is a biologically potent transcriptional coactivator and functions by binding to the PPXY motif present in several transcription factors. Notably, TAZ behaves as a transducer linking cytoplasmic signaling events to transcriptional regulation in the nucleus. Several different factors regulate TAZ expression and/or function. In particular, a major regulation of TAZ activity occurs through the Hippo pathway by a phosphorylation-mediated mechanism that causes its cytoplasmic sequestration or degradation.
  
  
  RESULTS
  Here we demonstrate that AMOTL2 robustly co-immunoprecipitates with TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N-terminus of AMOTL2. Furthermore, we show that AMOTL2 colocalizes with TAZ in the cytoplasm of H441 human lung cells and regulates TAZ cytoplasm-to-nucleus translocation through direct protein-protein interaction. Interestingly, the overexpression of AMOTL2 inhibits the functional cooperation between the transcription factor TTF-1 and TAZ on the Surfactant C gene promoter, as well as the expression of other known target genes of these regulatory factors.
  
  
  CONCLUSIONS
  Taken together, our results suggest an inhibitory role of AMOTL2 on TAZ ability to co-activate transcription and describe a different mechanism, Hippo pathway-independent, that modulates the activity of TAZ in lung cells through the interaction with Angiomotin-like 2 (AMOTL2).
authors.affiliation: CNR - National Research Council, Institute of Experimental Endocrinology and Oncology (IEOS), Naples, Italy. Electronic address: valeria.lucci@unina.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucci
authors.forename: Tina
authors.initials: T
authors.lastname: Di Palma
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Ambrosio
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Mariastella
authors.initials: M
authors.lastname: Zannini
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000091082:Angiomotins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: C508566:AMOTL2 protein, human; D000091082:Angiomotins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D037721:Pulmonary Surfactant-Associated Protein C; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human
keywords: AMOTL2; Angiomotin-like 2 protein; BMP4; CMV; DNA complementary to RNA; GST; Gene expression; HA; MLE; PBS; PCR; SP-A; SP-B, SP-C, surfactant protein A, B, C; Surfactant proteins; TAZ; TTF-1; Thyroid Transcription Factor-1; Transcriptional co-Activator with PDZ-binding motif; Transcriptional regulation; YAP; Yes-Associated Protein; bone morphogenetic protein 4; cDNA; cytomegalovirus; glutathione-S transferase; hemagglutinin; mouse lung epithelial; phosphate buffered saline; polymerase chain reaction