New Therapeutic Approach for Targeting Hippo Signalling Pathway

Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interacti...

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Autores principales: Domínguez Berrocal, Leticia, Cirri, Erica, Zhang, Xiguang, Andrini, Laura Beatriz, Marín, Gustavo Horacio, Lebel-Binay, Sophie, Rebollo, Angelita
Formato: Articulo
Lenguaje:Español
Publicado: 2019
Materias:
Ciencias Médicas
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/162149
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SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-162149
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spelling I19-R120-10915-1621492023-12-30T04:06:31Z http://sedici.unlp.edu.ar/handle/10915/162149 New Therapeutic Approach for Targeting Hippo Signalling Pathway Domínguez Berrocal, Leticia Cirri, Erica Zhang, Xiguang Andrini, Laura Beatriz Marín, Gustavo Horacio Lebel-Binay, Sophie Rebollo, Angelita 2019-03-18 2023-12-29T18:14:44Z es Ciencias Médicas Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interaction between TEAD and YAP, two transcription factors involved in the Hippo signalling pathway, whose deregulation is related to several types of cancer. We have validated the cell penetration and nuclear localization by flow cytometry and fluorescence microscopy and shown that the new generated peptide displays an apoptotic effect in tumor cell lines thanks to the specific nuclear delivery of the cargo, which targets a protein/protein interaction in the nucleus. In addition, the peptide has an anti-tumoral effect in vivo in xenograft models of breast cancer. The chimeric peptide designed in the current study shows encouraging prospects for developing nuclear anti- neoplastic drugs. Facultad de Ciencias Médicas Articulo Articulo http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Español
topic Ciencias Médicas
spellingShingle Ciencias Médicas
Domínguez Berrocal, Leticia
Cirri, Erica
Zhang, Xiguang
Andrini, Laura Beatriz
Marín, Gustavo Horacio
Lebel-Binay, Sophie
Rebollo, Angelita
New Therapeutic Approach for Targeting Hippo Signalling Pathway
topic_facet Ciencias Médicas
description Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interaction between TEAD and YAP, two transcription factors involved in the Hippo signalling pathway, whose deregulation is related to several types of cancer. We have validated the cell penetration and nuclear localization by flow cytometry and fluorescence microscopy and shown that the new generated peptide displays an apoptotic effect in tumor cell lines thanks to the specific nuclear delivery of the cargo, which targets a protein/protein interaction in the nucleus. In addition, the peptide has an anti-tumoral effect in vivo in xenograft models of breast cancer. The chimeric peptide designed in the current study shows encouraging prospects for developing nuclear anti- neoplastic drugs.
format Articulo
Articulo
author Domínguez Berrocal, Leticia
Cirri, Erica
Zhang, Xiguang
Andrini, Laura Beatriz
Marín, Gustavo Horacio
Lebel-Binay, Sophie
Rebollo, Angelita
author_facet Domínguez Berrocal, Leticia
Cirri, Erica
Zhang, Xiguang
Andrini, Laura Beatriz
Marín, Gustavo Horacio
Lebel-Binay, Sophie
Rebollo, Angelita
author_sort Domínguez Berrocal, Leticia
title New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_short New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_full New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_fullStr New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_full_unstemmed New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_sort new therapeutic approach for targeting hippo signalling pathway
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/162149
work_keys_str_mv AT dominguezberrocalleticia newtherapeuticapproachfortargetinghipposignallingpathway
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AT zhangxiguang newtherapeuticapproachfortargetinghipposignallingpathway
AT andrinilaurabeatriz newtherapeuticapproachfortargetinghipposignallingpathway
AT maringustavohoracio newtherapeuticapproachfortargetinghipposignallingpathway
AT lebelbinaysophie newtherapeuticapproachfortargetinghipposignallingpathway
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