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Interaction between the Cockayne syndrome B and p53 proteins: implications for aging
The CSB protein plays a role in the transcription coupled repair (TCR) branch of the nucleotide excision repair pathway. CSB is very often found mutated in Cockayne syndrome, a segmental progeroid genetic disease characterized by organ degeneration and growth failure. The tumor suppressor p53 plays...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314171/ https://www.ncbi.nlm.nih.gov/pubmed/22383384 |
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author | Frontini, Mattia Proietti-De-Santis, Luca |
author_facet | Frontini, Mattia Proietti-De-Santis, Luca |
author_sort | Frontini, Mattia |
collection | PubMed |
description | The CSB protein plays a role in the transcription coupled repair (TCR) branch of the nucleotide excision repair pathway. CSB is very often found mutated in Cockayne syndrome, a segmental progeroid genetic disease characterized by organ degeneration and growth failure. The tumor suppressor p53 plays a pivotal role in triggering senescence and apoptosis and suppressing tumorigenesis. Although p53 is very important to avoid cancer, its excessive activity can be detrimental for the lifespan of the organism. This is why a network of positive and negative feedback loops, which most likely evolved to fine-tune the activity of this tumor suppressor, modulate its induction and activation. Accordingly, an unbalanced p53 activity gives rise to premature aging or cancer. The physical interaction between CSB and p53 proteins has been known for more than a decade but, despite several hypotheses, nobody has been able to show the functional consequences of this interaction. In this review we resume recent advances towards a more comprehensive understanding of the critical role of this interaction in modulating p53's levels and activity, therefore helping the system find a reasonable equilibrium between the beneficial and the detrimental effects of its activity. This crosstalk re-establishes the physiological balance towards cell proliferation and survival instead of towards cell death, after stressors of a broad nature. Accordingly, cells bearing mutations in the csb gene are unable to re-establish this physiological balance and to properly respond to some stress stimuli and undergo massive apoptosis. |
format | Online Article Text |
id | pubmed-3314171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-33141712012-04-05 Interaction between the Cockayne syndrome B and p53 proteins: implications for aging Frontini, Mattia Proietti-De-Santis, Luca Aging (Albany NY) Review The CSB protein plays a role in the transcription coupled repair (TCR) branch of the nucleotide excision repair pathway. CSB is very often found mutated in Cockayne syndrome, a segmental progeroid genetic disease characterized by organ degeneration and growth failure. The tumor suppressor p53 plays a pivotal role in triggering senescence and apoptosis and suppressing tumorigenesis. Although p53 is very important to avoid cancer, its excessive activity can be detrimental for the lifespan of the organism. This is why a network of positive and negative feedback loops, which most likely evolved to fine-tune the activity of this tumor suppressor, modulate its induction and activation. Accordingly, an unbalanced p53 activity gives rise to premature aging or cancer. The physical interaction between CSB and p53 proteins has been known for more than a decade but, despite several hypotheses, nobody has been able to show the functional consequences of this interaction. In this review we resume recent advances towards a more comprehensive understanding of the critical role of this interaction in modulating p53's levels and activity, therefore helping the system find a reasonable equilibrium between the beneficial and the detrimental effects of its activity. This crosstalk re-establishes the physiological balance towards cell proliferation and survival instead of towards cell death, after stressors of a broad nature. Accordingly, cells bearing mutations in the csb gene are unable to re-establish this physiological balance and to properly respond to some stress stimuli and undergo massive apoptosis. Impact Journals LLC 2012-02-29 /pmc/articles/PMC3314171/ /pubmed/22383384 Text en Copyright: © 2012 Frontini and Proietti-De-Santis http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Review Frontini, Mattia Proietti-De-Santis, Luca Interaction between the Cockayne syndrome B and p53 proteins: implications for aging |
title | Interaction between the Cockayne syndrome B and p53 proteins: implications for aging |
title_full | Interaction between the Cockayne syndrome B and p53 proteins: implications for aging |
title_fullStr | Interaction between the Cockayne syndrome B and p53 proteins: implications for aging |
title_full_unstemmed | Interaction between the Cockayne syndrome B and p53 proteins: implications for aging |
title_short | Interaction between the Cockayne syndrome B and p53 proteins: implications for aging |
title_sort | interaction between the cockayne syndrome b and p53 proteins: implications for aging |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314171/ https://www.ncbi.nlm.nih.gov/pubmed/22383384 |
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