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PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylat...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807117/ https://www.ncbi.nlm.nih.gov/pubmed/35118387 http://dx.doi.org/10.1093/narcan/zcac002 |
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author | Tinsley, Samantha L Allen-Petersen, Brittany L |
author_facet | Tinsley, Samantha L Allen-Petersen, Brittany L |
author_sort | Tinsley, Samantha L |
collection | PubMed |
description | The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth. |
format | Online Article Text |
id | pubmed-8807117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88071172022-02-02 PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen Tinsley, Samantha L Allen-Petersen, Brittany L NAR Cancer Critical Reviews and Perspectives The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth. Oxford University Press 2022-02-01 /pmc/articles/PMC8807117/ /pubmed/35118387 http://dx.doi.org/10.1093/narcan/zcac002 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Critical Reviews and Perspectives Tinsley, Samantha L Allen-Petersen, Brittany L PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen |
title | PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen |
title_full | PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen |
title_fullStr | PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen |
title_full_unstemmed | PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen |
title_short | PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen |
title_sort | pp2a and cancer epigenetics: a therapeutic opportunity waiting to happen |
topic | Critical Reviews and Perspectives |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807117/ https://www.ncbi.nlm.nih.gov/pubmed/35118387 http://dx.doi.org/10.1093/narcan/zcac002 |
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