Lucci, Valeria (2011) Identification of new interactors of the transcriptional co-activator TAZ in human lung cells. [Tesi di dottorato] (Inedito)

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Identification of new interactors of the transcriptional co-activator TAZ in human lung cells
Autori:
AutoreEmail
Lucci, Valeriavaleria.lucci@unina.it
Data: 30 Novembre 2011
Numero di pagine: 47
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Biologia e patologia cellullare e molecolare "L. Califano"
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 24
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricoavvedim@unina.it
Tutor:
nomeemail
Zannini, Mariastellas.zannini@ieos.cnr.it
Data: 30 Novembre 2011
Numero di pagine: 47
Parole chiave: TAZ; AMOTL2; lung; transcriptional regulation
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Depositato il: 13 Dic 2011 11:33
Ultima modifica: 17 Giu 2014 06:03
URI: http://www.fedoa.unina.it/id/eprint/8861

Abstract

The Hippo pathway restricts the activity of transcriptional co-activators TAZ by phosphorylating it for cytoplasmic sequestration or degradation. In this report, we describe an independent mechanism for the cell to restrict the activity of TAZ through interaction with Angiomotin-like 2 (AMOTL2). AMOTL2 was robustly co- immunoprecipitated with FLAG-tagged TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N-terminus of AMOTL2. We demonstrate that AMOTL2 colocalizes with TAZ in the cytoplasm in H441 human lung cells and can regulate TAZ cytoplasm-to-nucleus translocation through direct protein- protein interaction in HeLa cells. Hippo refractory TAZ mutant (S89A) is also negatively regulated by AMOTL2. Since the expression of surfactant protein C, in the respiratory epithelial cells, is dependent on the cooperation of the transcription factor TTF-1 and TAZ, we used a luciferase report construct containing TTF-1 responsive elements identified in the SP-C promoter to verify if AMOTL2 inhibits transactivation properties of TAZ. The results of the luciferase assays suggested an inhibitory role of AMOTL2 on TAZ ability to co-activate transcription. These results reveal a novel mechanism to restrict the activity of TAZ through physical interaction with AMOTL2.

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