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Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer

KAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparativ...

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Autores principales: De Luca, Veronica, Leo, Manuela, Cretella, Elisabetta, Montanari, Arianna, Saliola, Michele, Ciaffi, Gabriele, Vecchione, Andrea, Stoppacciaro, Antonella, Filetici, Patrizia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140154/
https://www.ncbi.nlm.nih.gov/pubmed/35626719
http://dx.doi.org/10.3390/cells11101682
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author De Luca, Veronica
Leo, Manuela
Cretella, Elisabetta
Montanari, Arianna
Saliola, Michele
Ciaffi, Gabriele
Vecchione, Andrea
Stoppacciaro, Antonella
Filetici, Patrizia
author_facet De Luca, Veronica
Leo, Manuela
Cretella, Elisabetta
Montanari, Arianna
Saliola, Michele
Ciaffi, Gabriele
Vecchione, Andrea
Stoppacciaro, Antonella
Filetici, Patrizia
author_sort De Luca, Veronica
collection PubMed
description KAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparatively, the aggressive glioblastoma (GBM) multiforme tumor shows survival mechanisms able to overcome hypoxia in the brain. Starting from yeast and our findings on the role of Ubp8 in hypoxia, we extended our analysis to the human ortholog and signature cancer gene Usp22 in glioblastoma tumor specimens. Here we demonstrate that Usp22 is localized and overexpressed in the pseudo-palisade tissue around the necrotic area of the tumor. In addition, Usp22 colocalizes with the mitophagy marker Parkin, indicating a link with mitochondria function in GBM. Collectively, this evidence suggests that altered expression of Usp22 might provide a way for tumor cells to survive in hypoxic conditions, allowing the escape of cells from the necrotic area toward vascularized tissues. Collectively, our experimental data suggest a model for a possible mechanism of uncontrolled proliferation and invasion in glioblastoma.
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spelling pubmed-91401542022-05-28 Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer De Luca, Veronica Leo, Manuela Cretella, Elisabetta Montanari, Arianna Saliola, Michele Ciaffi, Gabriele Vecchione, Andrea Stoppacciaro, Antonella Filetici, Patrizia Cells Article KAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparatively, the aggressive glioblastoma (GBM) multiforme tumor shows survival mechanisms able to overcome hypoxia in the brain. Starting from yeast and our findings on the role of Ubp8 in hypoxia, we extended our analysis to the human ortholog and signature cancer gene Usp22 in glioblastoma tumor specimens. Here we demonstrate that Usp22 is localized and overexpressed in the pseudo-palisade tissue around the necrotic area of the tumor. In addition, Usp22 colocalizes with the mitophagy marker Parkin, indicating a link with mitochondria function in GBM. Collectively, this evidence suggests that altered expression of Usp22 might provide a way for tumor cells to survive in hypoxic conditions, allowing the escape of cells from the necrotic area toward vascularized tissues. Collectively, our experimental data suggest a model for a possible mechanism of uncontrolled proliferation and invasion in glioblastoma. MDPI 2022-05-19 /pmc/articles/PMC9140154/ /pubmed/35626719 http://dx.doi.org/10.3390/cells11101682 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
De Luca, Veronica
Leo, Manuela
Cretella, Elisabetta
Montanari, Arianna
Saliola, Michele
Ciaffi, Gabriele
Vecchione, Andrea
Stoppacciaro, Antonella
Filetici, Patrizia
Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
title Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
title_full Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
title_fullStr Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
title_full_unstemmed Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
title_short Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
title_sort role of yubp8 in mitochondria and hypoxia entangles the finding of human ortholog usp22 in the glioblastoma pseudo-palisade microlayer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140154/
https://www.ncbi.nlm.nih.gov/pubmed/35626719
http://dx.doi.org/10.3390/cells11101682
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