p53 Acetylation: Regulation and Consequences.
p53 Acetylation: Regulation and Consequences.
复制标题
DOI：
10.3390/cancers7010030
复制
发表时间：
2014-12-23
期刊：
影响因子：
5.2
通讯作者：
Quelle DE
中科院分区：
文献类型：
--
作者：
Reed SM;Quelle DE
p53的翻译后修饰在调节其肿瘤抑制功能中是关键的。例如，泛素化在决定p53稳定性、亚细胞定位和转录与非转录活性中起主要作用。对p53乙酰化的了解较少。它已被证明可以控制p53的转录活性，选择生长抑制与凋亡的基因靶点，以及响应于不同细胞损伤的生物学结果。然而，最近来自小鼠模型的体内证据质疑p53乙酰化（至少在某些位点）以及典型的p53功能（细胞周期停滞，衰老和凋亡）对肿瘤抑制的重要性。这篇综述讨论了关于p53乙酰化的累积研究结果，重点是修饰p53的乙酰转移酶及其活性调节机制。我们还评估了已知的p53的其他翻译后修饰对其乙酰化的影响，并总结了目前对p53乙酰化如何影响肿瘤抑制的展望。由于p53控制中的冗余，以及越来越多的人认识到个体修饰在很大程度上微调p53活性，而不是打开或关闭它，许多关于p53乙酰化在预防癌症中的生理重要性的问题仍然存在。
Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.
登录
查看更多内容
影响因子：
16
作者：
Charvet C;Wissler M;Brauns-Schubert P;Wang SJ;Tang Y;Sigloch FC;Mellert H;Brandenburg M;Lindner SE;Breit B;Green DR;McMahon SB;Borner C;Gu W;Maurer U
通讯作者：
Maurer U
影响因子：
3.9
作者：
Benkirane, Monsef;Sardet, Claude;Coux, Olivier
通讯作者：
Coux, Olivier
影响因子：
64.5
作者：
Avantaggiati, ML;Ogryzko, V;Kelly, K
通讯作者：
Kelly, K
影响因子：
64.5
作者：
Chakravarti, D;Ogryzko, V;Evans, RM
通讯作者：
Evans, RM
影响因子：
64.8
作者：
Bannister, AJ;Kouzarides, T
通讯作者：
Kouzarides, T