摘要
14-3-3是一类能够通过建立蛋白质 - 蛋白质相互作用(PPI)与多个靶标相互作用的蛋白质。它们通常存在于所有真核生物中,具有保守的二级结构和高度序列同源性。 14-3-3蛋白通过触发或干扰特定蛋白质伙伴的活性参与许多生理和病理性细胞过程。在过去的几年中,科学界已经收集了七种人类14-3-3同种型在癌症或神经退行性疾病中所起的作用的许多证据。实际上,这些蛋白质通过与(i)致癌蛋白和(ii)促凋亡蛋白和(iii)与帕金森病和阿尔茨海默病相关的蛋白相互作用来调节与这些疾病相关的分子机制。 14-3-3PPI的小分子调节剂的发现可以促进对这些蛋白质的生理学作用的完整理解,并且可以为这些关键的病理状态提供有价值的治疗方法
关键词: 14-3-3,癌症,神经变性,蛋白质 - 蛋白质相互作用,小分子,药物发现,磷酸化。
Current Medicinal Chemistry
Title:Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update
Volume: 25 Issue: 1
关键词: 14-3-3,癌症,神经变性,蛋白质 - 蛋白质相互作用,小分子,药物发现,磷酸化。
摘要: 14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.
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Cite this article as:
Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update, Current Medicinal Chemistry 2018; 25 (1) . https://dx.doi.org/10.2174/0929867324666170426095015
DOI https://dx.doi.org/10.2174/0929867324666170426095015 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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