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Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence

Cellular senescence plays essential roles in tissue homeostasis as well as a host of diseases ranging from cancers to age-related neurodegeneration. Various molecular pathways can induce senescence and these different pathways dictate the phenotypic and metabolic changes that accompany the transitio...

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Autores principales: Plafker, Kendra S., Zyla, Katarzyna, Berry, William, Plafker, Scott M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007080/
https://www.ncbi.nlm.nih.gov/pubmed/29879550
http://dx.doi.org/10.1016/j.redox.2018.05.008
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author Plafker, Kendra S.
Zyla, Katarzyna
Berry, William
Plafker, Scott M.
author_facet Plafker, Kendra S.
Zyla, Katarzyna
Berry, William
Plafker, Scott M.
author_sort Plafker, Kendra S.
collection PubMed
description Cellular senescence plays essential roles in tissue homeostasis as well as a host of diseases ranging from cancers to age-related neurodegeneration. Various molecular pathways can induce senescence and these different pathways dictate the phenotypic and metabolic changes that accompany the transition to, and maintenance of, the senescence state. Here, we describe a novel senescence phenotype induced by depletion of UBE2E3, a highly-conserved, metazoan ubiquitin conjugating enzyme. Cells depleted of UBE2E3 become senescent in the absence of overt DNA damage and have a distinct senescence-associated secretory phenotype, increased mitochondrial and lysosomal mass, an increased sensitivity to mitochondrial and lysosomal poisons, and an increased basal autophagic flux. This senescence phenotype can be partially suppressed by co-depletion of either p53 or its cognate target gene, p21(CIP1/WAF1), or by co-depleting the tumor suppressor p16(INK4a). Together, these data describe a direct link of a ubiquitin conjugating enzyme to cellular senescence and further underscore the consequences of disrupting the integration between the ubiquitin proteolysis system and the autophagy machinery.
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spelling pubmed-60070802018-06-20 Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence Plafker, Kendra S. Zyla, Katarzyna Berry, William Plafker, Scott M. Redox Biol Research Paper Cellular senescence plays essential roles in tissue homeostasis as well as a host of diseases ranging from cancers to age-related neurodegeneration. Various molecular pathways can induce senescence and these different pathways dictate the phenotypic and metabolic changes that accompany the transition to, and maintenance of, the senescence state. Here, we describe a novel senescence phenotype induced by depletion of UBE2E3, a highly-conserved, metazoan ubiquitin conjugating enzyme. Cells depleted of UBE2E3 become senescent in the absence of overt DNA damage and have a distinct senescence-associated secretory phenotype, increased mitochondrial and lysosomal mass, an increased sensitivity to mitochondrial and lysosomal poisons, and an increased basal autophagic flux. This senescence phenotype can be partially suppressed by co-depletion of either p53 or its cognate target gene, p21(CIP1/WAF1), or by co-depleting the tumor suppressor p16(INK4a). Together, these data describe a direct link of a ubiquitin conjugating enzyme to cellular senescence and further underscore the consequences of disrupting the integration between the ubiquitin proteolysis system and the autophagy machinery. Elsevier 2018-05-21 /pmc/articles/PMC6007080/ /pubmed/29879550 http://dx.doi.org/10.1016/j.redox.2018.05.008 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Plafker, Kendra S.
Zyla, Katarzyna
Berry, William
Plafker, Scott M.
Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
title Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
title_full Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
title_fullStr Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
title_full_unstemmed Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
title_short Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
title_sort loss of the ubiquitin conjugating enzyme ube2e3 induces cellular senescence
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007080/
https://www.ncbi.nlm.nih.gov/pubmed/29879550
http://dx.doi.org/10.1016/j.redox.2018.05.008
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