Deciphering the acetylation code of p53 in transcription regulation and tumor suppression.
Deciphering the acetylation code of p53 in transcription regulation and tumor suppression.
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破译转录调节和肿瘤抑制中p53的乙酰化密码。
DOI：
10.1038/s41388-022-02331-9
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发表时间：
2022-05
期刊：
影响因子：
8
通讯作者：
Gu, Wei
中科院分区：
文献类型：
--
作者：
Xia, Zhangchuan;Kon, Ning;Gu, Alyssa P.;Tavana, Omid;Gu, Wei
虽然众所周知，P53介导的肿瘤抑制主要是通过其转录调控能力发挥作用的，但这种调控的分子机制还不完全清楚。在众多的调控方式中，P53的乙酰化引起了人们的极大兴趣。P53是最早被发现受乙酰化和去乙酰化调节的非组蛋白蛋白之一，后来的工作证实可逆组蛋白乙酰化是调节非组蛋白蛋白的一般机制。与应激反应中发生的其他类型的翻译后修饰不同，最近通过使用具有乙酰化缺陷和乙酰化模拟突变体的敲门小鼠在体内验证了p53乙酰化的作用。在这里，我们回顾了乙酰化在P53介导的活性中的作用，重点是在肿瘤抑制过程中，哪些特定的乙酰化位点对P53依赖的转录调控至关重要，以及P53的乙酰化如何招募特定的“读者”来执行其对不同靶点的启动子特异性调节。我们还讨论了P53乙酰化在差异调节其在细胞周期停滞、衰老和凋亡中的经典活性中的作用，以及新发现的非常规功能，如细胞代谢和铁下垂。
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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DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
14.9
作者：
Chen R;Liu Y;Zhuang H;Yang B;Hei K;Xiao M;Hou C;Gao H;Zhang X;Jia C;Li L;Li Y;Zhang N
通讯作者：
Zhang N
影响因子：
64.5
作者：
Avantaggiati, ML;Ogryzko, V;Kelly, K
通讯作者：
Kelly, K
影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias