Functional mimicry of the acetylated C-terminal tail of p53 by a SUMO-1 acetylated domain, SAD.
Functional mimicry of the acetylated C-terminal tail of p53 by a SUMO-1 acetylated domain, SAD.
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DOI：
10.1002/jcp.22224
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发表时间：
2010-11
影响因子：
5.6
通讯作者：
Avantaggiati, Maria Laura
中科院分区：
文献类型：
--
作者：
Cheema, Amrita;Knights, Chad D.;Rao, Mahadev;Catania, Jason;Perez, Ricardo;Simons, Brigitte;Dakshanamurthy, Sivanesan;Kolukula, Vamsi K.;Tilli, Maddalena;Furth, Priscilla A.;Albanese, Christopher;Avantaggiati, Maria Laura
泛素样分子SUMO-1是一种对多种生物学过程至关重要的小蛋白质，它与许多细胞内蛋白质共价结合，特别是与转录机制的调节组分如组蛋白和转录因子共价结合。SUMO化为增殖和转录提供了刺激或抑制信号，但SUMO-1实现这种多功能性作用的分子机制尚未完全确定。肿瘤抑制因子和转录调节因子p53是相关的SUMO-1靶点。特别地，p53的C-末端尾部经历类小泛素化和乙酰化。虽然类小泛素化的作用仍有争议，乙酰化修饰p53与染色质嵌入的启动子的相互作用，并强制p53凋亡活性。在这项研究中，我们表明，SUMO-1的N-末端区域可能在功能上模仿这种活性的p53 C-末端尾巴。我们发现这个SUMO-1结构域与C-末端可乙酰化的p53尾部以及其他转录因子的可乙酰化结构域具有相似性。SUMO-1在与其底物和p53缀合时确实是乙酰化的。在可乙酰化的形式中，SUMO-1通过修饰p53转录程序、通过促进与所选启动子的结合以及通过促进细胞凋亡来调节p53应答。相比之下，当非乙酰化时，SUMO-1强制细胞周期停滞和p53与不同的基因组结合。这些数据首次证明SUMO-1，一种翻译后修饰，反过来，通过乙酰化修饰。此外，它们暗示SUMO-1影响各种细胞结果的多效性效应和p53的活性取决于其乙酰化状态。
The ubiquitin-like molecule, SUMO-1, a small protein essential for a variety of biological processes, is covalently conjugated to many intracellular proteins, especially to regulatory components of the transcriptional machinery, such as histones and transcription factors. Sumoylation provides either a stimulatory or an inhibitory signal for proliferation and for transcription, but the molecular mechanisms by which SUMO-1 achieves such versatility of effects are incompletely defined. The tumor suppressor and transcription regulator p53 is a relevant SUMO-1 target. Particularly, the C-terminal tail of p53 undergoes both sumoylation and acetylation. While the effects of sumoylation are still controversial, acetylation modifies p53 interaction with chromatin embedded promoters, and enforces p53 apoptotic activity. In this study, we show that the N-terminal region of SUMO-1 might functionally mimic this activity of the p53 C-terminal tail. We found that this SUMO-1 domain possesses similarity with the C-terminal acetylable p53 tail as well as with acetylable domains of other transcription factors. SUMO-1 is, indeed, acetylated when conjugated to its substrates and to p53. In the acetylable form SUMO-1 tunes the p53 response by modifying p53 transcriptional program, by promoting binding onto selected promoters and by favoring apoptosis. By contrast, when non-acetylable, SUMO-1 enforces cell-cycle arrest and p53 binding to a different sets of genes. These data demonstrate for the first time that SUMO-1, a post-translational modification is, in turn, modified by acetylation. Further, they imply that the pleiotropy of effects by which SUMO-1 influences various cellular outcomes and the activity of p53 depends upon its acetylation state.
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影响因子：
3.8
作者：
Heideker, J.;Perry, J. J. P.;Boddy, M. N.
通讯作者：
Boddy, M. N.
DOI：
10.1073/pnas.0401002101
发表时间：
2004-05-11
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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