Decision Making by p53: Life versus Death.
Decision Making by p53: Life versus Death.
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发表时间：
2010
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通讯作者：
Lingyan Jiang;M. Sheikh;Ying Huang
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作者：
Lingyan Jiang;M. Sheikh;Ying Huang
细胞对DNA损伤的反应本质上是多因素的，涉及一个复杂的信号网络，在这个网络中，P53起着聚合信号的“分子节点”的作用。P53参与了多种细胞过程，主要作为转录因子发挥作用，也以转录非依赖的方式发挥作用。它在DNA损伤后被迅速激活，磷酸化是起始信号之一。细胞环境以及DNA损伤的类型和严重程度决定了P53的激活密码，其活性主要通过蛋白质降解、翻译后修饰和与各种细胞辅助因子的相互作用来调节。这些事件在P53的决策中至关重要，因为它具有接收、评估和整合不同信号并相应地传递它们以诱导细胞死亡或促进细胞存活的能力。在这个决策过程中，它的转录作用是激活与诱导细胞周期停滞或凋亡相关的特定靶基因子集，这一点是至关重要的，并通过其转录无关功能进行进一步微调。本文综述了关于P53在决定DNA损伤细胞命运中的作用的知识现状。
Cellular response to DNA damage is multifacted in nature and involves a complex signaling network in which p53 functions as a "molecular node" for converging signals. p53 has been implicated in a variety of cellular processes primarily functioning as a transcription factor and also in a transcription-independent manner. It is rapidly activated following DNA damage with phosphorylation as one of the initial signals. Cellular context as well as the type and severity of DNA damage determine p53 activation code, and its activities are regulated predominantly through protein degradation, post-translational modification and interactions with various cellular co-factors. These events are crucial in decision making by p53 as it has the ability to receive, assess and integrate different signals and route them accordingly to induce cell death or promote cell survival. In this decision making process, its transcriptional role to activate a specific subset of target genes linked to inducing cell cycle arrest or apoptosis is critical that is further fine-tuned by its transcription-independent function. This article reviews the current state of knowledge about the role of p53 in determining the fate of cells that have incurred DNA damage.