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Premature aging and cancer development in transgenic mice lacking functional CYLD
CYLD is a deubiquitinating enzyme known for its role as a tumor suppressor whose mutation leads to skin appendages tumors and other cancers. In this manuscript we report that the tumor suppressor CYLD, similarly to other renowned tumor suppressor genes, protects from premature aging and cancer. We h...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339805/ https://www.ncbi.nlm.nih.gov/pubmed/30631004 http://dx.doi.org/10.18632/aging.101732 |
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author | Alameda, Josefa P. Ramírez, Ángel García-Fernández, Rosa A. Navarro, Manuel Page, Angustias Segovia, José C. Sanchez, Rebeca Suárez-Cabrera, Cristian Paramio, Jesús M. Bravo, Ana Fernández-Aceñero, M. Jesús Casanova, M. Llanos |
author_facet | Alameda, Josefa P. Ramírez, Ángel García-Fernández, Rosa A. Navarro, Manuel Page, Angustias Segovia, José C. Sanchez, Rebeca Suárez-Cabrera, Cristian Paramio, Jesús M. Bravo, Ana Fernández-Aceñero, M. Jesús Casanova, M. Llanos |
author_sort | Alameda, Josefa P. |
collection | PubMed |
description | CYLD is a deubiquitinating enzyme known for its role as a tumor suppressor whose mutation leads to skin appendages tumors and other cancers. In this manuscript we report that the tumor suppressor CYLD, similarly to other renowned tumor suppressor genes, protects from premature aging and cancer. We have generated transgenic mice expressing the mutant CYLD(C/S) protein, lacking its deubiquitinase function, under the control of the keratin 5 promoter, the K5-CYLD(C/S) mice. These mice express the transgene in different organs, including those considered to be more susceptible to aging, such as skin and thymus. Our results show that K5-CYLD(C/S) mice exhibit epidermal, hair follicle, and sebaceous gland alterations; and, importantly, they show signs of premature aging from an early age. Typically, 3-month-old K5-CYLD(C/S) mice exhibit a phenotype characterized by alopecia and kyphosis, and, the histological examination reveals that transgenic mice show signs of accelerated aging in numerous organs such as skin, thymus, pancreas, liver and lung. Additionally, they spontaneously develop tumors of diverse origin. Over-activation of the NF-κB pathway, along with hyperactivation of Akt, JNK and c-Myc, and chronic inflammation, appear as the mechanisms responsible for the premature aging of the K5-CYLD(C/S) mice. |
format | Online Article Text |
id | pubmed-6339805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-63398052019-01-28 Premature aging and cancer development in transgenic mice lacking functional CYLD Alameda, Josefa P. Ramírez, Ángel García-Fernández, Rosa A. Navarro, Manuel Page, Angustias Segovia, José C. Sanchez, Rebeca Suárez-Cabrera, Cristian Paramio, Jesús M. Bravo, Ana Fernández-Aceñero, M. Jesús Casanova, M. Llanos Aging (Albany NY) Research Paper CYLD is a deubiquitinating enzyme known for its role as a tumor suppressor whose mutation leads to skin appendages tumors and other cancers. In this manuscript we report that the tumor suppressor CYLD, similarly to other renowned tumor suppressor genes, protects from premature aging and cancer. We have generated transgenic mice expressing the mutant CYLD(C/S) protein, lacking its deubiquitinase function, under the control of the keratin 5 promoter, the K5-CYLD(C/S) mice. These mice express the transgene in different organs, including those considered to be more susceptible to aging, such as skin and thymus. Our results show that K5-CYLD(C/S) mice exhibit epidermal, hair follicle, and sebaceous gland alterations; and, importantly, they show signs of premature aging from an early age. Typically, 3-month-old K5-CYLD(C/S) mice exhibit a phenotype characterized by alopecia and kyphosis, and, the histological examination reveals that transgenic mice show signs of accelerated aging in numerous organs such as skin, thymus, pancreas, liver and lung. Additionally, they spontaneously develop tumors of diverse origin. Over-activation of the NF-κB pathway, along with hyperactivation of Akt, JNK and c-Myc, and chronic inflammation, appear as the mechanisms responsible for the premature aging of the K5-CYLD(C/S) mice. Impact Journals 2019-01-10 /pmc/articles/PMC6339805/ /pubmed/30631004 http://dx.doi.org/10.18632/aging.101732 Text en Copyright © 2019 Alameda et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Alameda, Josefa P. Ramírez, Ángel García-Fernández, Rosa A. Navarro, Manuel Page, Angustias Segovia, José C. Sanchez, Rebeca Suárez-Cabrera, Cristian Paramio, Jesús M. Bravo, Ana Fernández-Aceñero, M. Jesús Casanova, M. Llanos Premature aging and cancer development in transgenic mice lacking functional CYLD |
title | Premature aging and cancer development in transgenic mice lacking functional CYLD |
title_full | Premature aging and cancer development in transgenic mice lacking functional CYLD |
title_fullStr | Premature aging and cancer development in transgenic mice lacking functional CYLD |
title_full_unstemmed | Premature aging and cancer development in transgenic mice lacking functional CYLD |
title_short | Premature aging and cancer development in transgenic mice lacking functional CYLD |
title_sort | premature aging and cancer development in transgenic mice lacking functional cyld |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339805/ https://www.ncbi.nlm.nih.gov/pubmed/30631004 http://dx.doi.org/10.18632/aging.101732 |
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