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Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors
Ribosome biogenesis is an emerging therapeutic target. It has been proposed that cancer cells are addicted to ribosome production which is therefore considered a druggable pathway in cancer therapy. Cancer cells have been shown to be more sensitive to inhibition of the ribosome production than healt...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440923/ https://www.ncbi.nlm.nih.gov/pubmed/34540895 http://dx.doi.org/10.3389/fmolb.2021.718941 |
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author | Orea-Ordóñez, Lidia Masiá, Susana Bravo, Jerónimo |
author_facet | Orea-Ordóñez, Lidia Masiá, Susana Bravo, Jerónimo |
author_sort | Orea-Ordóñez, Lidia |
collection | PubMed |
description | Ribosome biogenesis is an emerging therapeutic target. It has been proposed that cancer cells are addicted to ribosome production which is therefore considered a druggable pathway in cancer therapy. Cancer cells have been shown to be more sensitive to inhibition of the ribosome production than healthy cells. Initial attempts of inhibiting ribosome biogenesis have been focused on the inhibition of transcription by targeting RNA Pol I. Despite being a promising field of research, several limitations have been identified during the development of RNA Pol I inhibitors, like the lack of specificity or acquired resistance. Ribosome biogenesis is a multistep process and additional points of intervention, downstream the very initial stage, could be investigated. Eukaryotic ribosome maturation involves the participation of more than 200 essential assembly factors that will not be part of the final mature ribosome and frequently require protein–protein interactions to exert their biological action. Using mutagenesis, we have previously shown that alteration of the complex interface between assembly factors impairs proper ribosome maturation in yeast. As a first step toward the developing of ribosome biogenesis inhibitory tools, we have used our previously solved crystal structure of the Chaetomium thermophilum complex between the assembly factors Erb1 and Ytm1 to perform a structure-guided selection of interference peptides. The peptides have been assayed in vitro for their ability to bind their cellular partner using biophysical techniques. |
format | Online Article Text |
id | pubmed-8440923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84409232021-09-16 Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors Orea-Ordóñez, Lidia Masiá, Susana Bravo, Jerónimo Front Mol Biosci Molecular Biosciences Ribosome biogenesis is an emerging therapeutic target. It has been proposed that cancer cells are addicted to ribosome production which is therefore considered a druggable pathway in cancer therapy. Cancer cells have been shown to be more sensitive to inhibition of the ribosome production than healthy cells. Initial attempts of inhibiting ribosome biogenesis have been focused on the inhibition of transcription by targeting RNA Pol I. Despite being a promising field of research, several limitations have been identified during the development of RNA Pol I inhibitors, like the lack of specificity or acquired resistance. Ribosome biogenesis is a multistep process and additional points of intervention, downstream the very initial stage, could be investigated. Eukaryotic ribosome maturation involves the participation of more than 200 essential assembly factors that will not be part of the final mature ribosome and frequently require protein–protein interactions to exert their biological action. Using mutagenesis, we have previously shown that alteration of the complex interface between assembly factors impairs proper ribosome maturation in yeast. As a first step toward the developing of ribosome biogenesis inhibitory tools, we have used our previously solved crystal structure of the Chaetomium thermophilum complex between the assembly factors Erb1 and Ytm1 to perform a structure-guided selection of interference peptides. The peptides have been assayed in vitro for their ability to bind their cellular partner using biophysical techniques. Frontiers Media S.A. 2021-09-01 /pmc/articles/PMC8440923/ /pubmed/34540895 http://dx.doi.org/10.3389/fmolb.2021.718941 Text en Copyright © 2021 Orea-Ordóñez, Masiá and Bravo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Orea-Ordóñez, Lidia Masiá, Susana Bravo, Jerónimo Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors |
title | Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors |
title_full | Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors |
title_fullStr | Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors |
title_full_unstemmed | Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors |
title_short | Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors |
title_sort | peptides targeting the interaction between erb1 and ytm1 ribosome assembly factors |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440923/ https://www.ncbi.nlm.nih.gov/pubmed/34540895 http://dx.doi.org/10.3389/fmolb.2021.718941 |
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