AMOTL2 interaction with TAZ causes the inhibition of surfactant proteins expression in lung cells.
Gene
; 529(2): 300-6, 2013 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-23911299
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).Palavras-chave
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
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Proteínas de Transporte
/
Proteína C Associada a Surfactante Pulmonar
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Pulmão
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article