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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
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.
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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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