PP2A和癌症表观遗传学:一个等待发生的治疗机会。

NAR Cancer Pub Date : 2022-02-01 eCollection Date: 2022-03-01 DOI:10.1093/narcan/zcac002
Samantha L Tinsley, Brittany L Allen-Petersen
{"title":"PP2A和癌症表观遗传学:一个等待发生的治疗机会。","authors":"Samantha L Tinsley,&nbsp;Brittany L Allen-Petersen","doi":"10.1093/narcan/zcac002","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807117/pdf/","citationCount":"9","resultStr":"{\"title\":\"PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen.\",\"authors\":\"Samantha L Tinsley,&nbsp;Brittany L Allen-Petersen\",\"doi\":\"10.1093/narcan/zcac002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":18879,\"journal\":{\"name\":\"NAR Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807117/pdf/\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NAR Cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/narcan/zcac002\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/3/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NAR Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/narcan/zcac002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/3/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 9

摘要

染色质的表观遗传状态被调节因子改变,这些调节因子影响基因表达以响应环境刺激。虽然一些翻译后修饰有助于染色质可及性和转录程序,但我们对特定磷酸化位点的作用的理解是有限的。在癌症中,激酶和磷酸酶通常被解除调控,导致致癌信号的增加和表观遗传调控的丧失。已知异常的表观遗传状态可促进许多癌症类型的细胞可塑性和治疗耐药性的发展,突出了这些机制对癌细胞表型的重要性。蛋白磷酸酶2A (PP2A)是一种针对多种细胞蛋白的异源三聚体全酶。PP2A复合物的组成影响其细胞靶标和活性。因此,PP2A可以抑制肿瘤或致癌取决于细胞环境。了解PP2A调控的细微差别及其对表观遗传改变的影响可以带来新的治疗途径,提供更多的特异性,并有助于肿瘤领域个性化医疗的发展。在这篇综述中,我们总结了已知的pp2a调节底物和潜在的磷酸化位点,这些磷酸化位点有助于癌细胞的表观遗传学,以及利用这种磷酸酶来抑制肿瘤生长的可能策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen.

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen.

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen.

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 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信