An insight into the life of p53: a protein coping with many functions! Review of the 9th p53 Workshop, Crete, May 9-13, 1998.
An insight into the life of p53: a protein coping with many functions! Review of the 9th p53 Workshop, Crete, May 9-13, 1998.
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深入了解 p53 的生命：一种具有多种功能的蛋白质！
DOI：
10.1016/s0304-419x(98)00024-9
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
V. Rotter
中科院分区：
文献类型：
--
作者：
N. Almog;V. Rotter
克里特岛被选为一年一度的p53研究庆祝活动。尽管这种分子被发现已经将近20年了[1，2]，人们对它的生物学特性也有了很多了解[3^7]，但关于这种蛋白质的功能的分子机制以及它所参与的生理途径，仍然存在一些悬而未决的问题。然而，很明显，癌细胞中最常见的突变基因P53确实是癌症研究的主要目标。一方面，设计高效、高效的方法恢复肿瘤细胞中失去的野生型p53抑制活性，另一方面取消突变型p53的表达，这在超过50%的人类原代肿瘤细胞中很明显[9，10]，仍然是未来的主要目标。这次会议讨论了P53调控及其功能的几个有趣的方面，并提出了控制蛋白质稳定和激活的新机制。影响P53行为的一系列复杂事件似乎正在扩大。讨论了该分子的结构特征及其与其他蛋白质配对的相互关系。在这里，我们总结本次会议提出的主要新进展和概念进展2。自两年前在邓迪的上一次P53研讨会以来，我们对P53的激活方式和此后的生化功能的理解取得了进展。特别是，在阐明遗传毒性应激后导致P53蛋白稳定和激活的途径方面有了显著的进展。越来越多的证据表明，P53蛋白的翻译后修饰以及与不同细胞蛋白的特异性相互作用是导致分子多样性的两种机制，使单个基因能够处理P53蛋白的多种功能。值得一提的是，多态P53物种以及选择性剪接的P53蛋白[11]的存在也可能是功能异质性的原因。
The island of Crete was chosen for the annual celebration of p53 research. Although almost 20 years have passed since the molecule was órst discovered [1, 2], and much has been learnt about its biological characteristics [3^ 7] there are still open questions regarding the molecular mechanisms that underlie the functions of this protein as well as the physiological pathways in which it takes part. Nevertheless, it is clear that p53, the most commonly mutated gene in cancer cells [8], is indeed a prime target in cancer research. Designing efficient and productive ways for restoring the lost wild-type p53 suppressor activity in tumor cells on one hand and abolishing the expression of mutant p53, evident in more than 50% of human primary tumor cells [9, 10] on the other, are still central future goals. Several interesting aspects of p53 regulation and of its function were discussed in this meeting, and novel mechanisms controlling protein stability and activation were presented. The complex array of events which affect p53 behavior seem to be expanding. Structural features of the molecule and its interrelations with other protein partners were also discussed. Here, we summarize the major new óndings and conceptual advances presented in this meeting.2. p53: differenthats' for the same proteinSince the last p53 workshop in Dundee two years ago, there have been advances in our understanding of the ways in which p53 is activated and functions biochemically thereafter. In particular, there were signiócant developments in clarifying the pathways leading to p53 protein stabilization and activation following genotoxic stress. A growing body of evidence suggests that posttranslational modiócations of the p53 protein, as well as specióc interactions with distinct cellular proteins, are two mechanisms responsible for the molecular versatility that enables a single gene to address the multiple functions attributed to the p53 protein. It is worth mentioning that the existence of polymorphic p53 species as well as alternatively spliced p53 proteins [11] may also account for functional heterogeneity.