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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423280/ https://www.ncbi.nlm.nih.gov/pubmed/30886324 http://dx.doi.org/10.1038/s41598-019-41404-w |
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author | Dominguez-Berrocal, Leticia Cirri, Erica Zhang, Xiguang Andrini, Laura Marin, Gustavo H. Lebel-Binay, Sophie Rebollo, Angelita |
author_facet | Dominguez-Berrocal, Leticia Cirri, Erica Zhang, Xiguang Andrini, Laura Marin, Gustavo H. Lebel-Binay, Sophie Rebollo, Angelita |
author_sort | Dominguez-Berrocal, Leticia |
collection | PubMed |
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 | Online Article Text |
id | pubmed-6423280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64232802019-03-26 New Therapeutic Approach for Targeting Hippo Signalling Pathway Dominguez-Berrocal, Leticia Cirri, Erica Zhang, Xiguang Andrini, Laura Marin, Gustavo H. Lebel-Binay, Sophie Rebollo, Angelita Sci Rep Article 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. Nature Publishing Group UK 2019-03-18 /pmc/articles/PMC6423280/ /pubmed/30886324 http://dx.doi.org/10.1038/s41598-019-41404-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dominguez-Berrocal, Leticia Cirri, Erica Zhang, Xiguang Andrini, Laura Marin, Gustavo H. Lebel-Binay, Sophie Rebollo, Angelita New Therapeutic Approach for Targeting Hippo Signalling Pathway |
title | 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_short | New Therapeutic Approach for Targeting Hippo Signalling Pathway |
title_sort | new therapeutic approach for targeting hippo signalling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423280/ https://www.ncbi.nlm.nih.gov/pubmed/30886324 http://dx.doi.org/10.1038/s41598-019-41404-w |
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