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Deciphering the acetylation code of p53 in transcription regulation and tumor suppression

Although it is well established that p53-mediated tumor suppression mainly acts through its ability in transcriptional regulation, the molecular mechanisms of this regulation are not completely understood. Among a number of regulatory modes, acetylation of p53 attracts great interests. p53 was one o...

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Autores principales: Xia, Zhangchuan, Kon, Ning, Gu, Alyssa P., Tavana, Omid, Gu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149126/
https://www.ncbi.nlm.nih.gov/pubmed/35487975
http://dx.doi.org/10.1038/s41388-022-02331-9
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author Xia, Zhangchuan
Kon, Ning
Gu, Alyssa P.
Tavana, Omid
Gu, Wei
author_facet Xia, Zhangchuan
Kon, Ning
Gu, Alyssa P.
Tavana, Omid
Gu, Wei
author_sort Xia, Zhangchuan
collection PubMed
description Although it is well established that p53-mediated tumor suppression mainly acts through its ability in transcriptional regulation, the molecular mechanisms of this regulation are not completely understood. Among a number of regulatory modes, acetylation of p53 attracts great interests. p53 was one of the first non-histone proteins found to be functionally regulated by acetylation and deacetylation, and subsequent work has established that reversible acetylation is a general mechanism for regulation of non-histone proteins. Unlike other types of post-translational modifications occurred during stress responses, the role of p53 acetylation has been recently validated in vivo by using the knockin mice with both acetylation-defective and acetylation-mimicking p53 mutants. Here, we review the role of acetylation in p53-mediated activities, with a focus on which specific acetylation sites are critical for p53-dependent transcription regulation during tumor suppression and how acetylation of p53 recruits specific “readers” to execute its promoter-specific regulation of different targets. We also discuss the role of p53 acetylation in differentially regulating its classic activities in cell cycle arrest, senescence and apoptosis as well as newly identified unconventional functions such as cell metabolism and ferroptosis.
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spelling pubmed-91491262022-10-29 Deciphering the acetylation code of p53 in transcription regulation and tumor suppression Xia, Zhangchuan Kon, Ning Gu, Alyssa P. Tavana, Omid Gu, Wei Oncogene Article Although it is well established that p53-mediated tumor suppression mainly acts through its ability in transcriptional regulation, the molecular mechanisms of this regulation are not completely understood. Among a number of regulatory modes, acetylation of p53 attracts great interests. p53 was one of the first non-histone proteins found to be functionally regulated by acetylation and deacetylation, and subsequent work has established that reversible acetylation is a general mechanism for regulation of non-histone proteins. Unlike other types of post-translational modifications occurred during stress responses, the role of p53 acetylation has been recently validated in vivo by using the knockin mice with both acetylation-defective and acetylation-mimicking p53 mutants. Here, we review the role of acetylation in p53-mediated activities, with a focus on which specific acetylation sites are critical for p53-dependent transcription regulation during tumor suppression and how acetylation of p53 recruits specific “readers” to execute its promoter-specific regulation of different targets. We also discuss the role of p53 acetylation in differentially regulating its classic activities in cell cycle arrest, senescence and apoptosis as well as newly identified unconventional functions such as cell metabolism and ferroptosis. 2022-05 2022-04-29 /pmc/articles/PMC9149126/ /pubmed/35487975 http://dx.doi.org/10.1038/s41388-022-02331-9 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Xia, Zhangchuan
Kon, Ning
Gu, Alyssa P.
Tavana, Omid
Gu, Wei
Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
title Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
title_full Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
title_fullStr Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
title_full_unstemmed Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
title_short Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
title_sort deciphering the acetylation code of p53 in transcription regulation and tumor suppression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149126/
https://www.ncbi.nlm.nih.gov/pubmed/35487975
http://dx.doi.org/10.1038/s41388-022-02331-9
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