Protein-protein interactions and cancer: targeting the central dogma.
Protein-protein interactions and cancer: targeting the central dogma.
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DOI：
10.2174/156802611794072614
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发表时间：
2011-01
影响因子：
3.4
通讯作者：
A. Garner;K. Janda
中科院分区：
文献类型：
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作者：
A. Garner;K. Janda
据预测，人类相互作用组中存在40，000至200，000种蛋白质-蛋白质相互作用。由于这些相互作用在许多重要的细胞功能中具有关键性质，并且它们的失调是疾病的原因，因此这些结合事件的调节已经成为领先的但困难的治疗竞技场。特别地，靶向与癌症相关的蛋白质-蛋白质相互作用具有根本重要性，因为在癌状态中几种异常表达的蛋白质的肿瘤促进功能是其与蛋白质结合配偶体相互作用的能力的直接结果。重要的是，这些蛋白质复合物在分子生物学中心法则的每一个步骤中都发挥着至关重要的作用，这是遗传传递的基本过程。随着对这些遗传过程的机制的许多重要发现，需要鉴定新的化学探针以更好地理解和验证与中心法则相关的蛋白质-蛋白质相互作用的可药用性。在这篇综述中，我们提供了一个概述目前的小分子为基础的蛋白质-蛋白质相互作用抑制剂的每个阶段的中心法则：转录，mRNA剪接和翻译。重要的是，通过我们的分析，我们发现缺乏靶向mRNA剪接和翻译的必要探针，从而为这些领域的扩展开辟了可能性。
Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.