Cau Ylenia, Valensin Daniela, Mori Mattia, Draghi Sara, Botta Maurizio
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, Siena. Italy.
Curr Med Chem. 2018;25(1):5-21. doi: 10.2174/0929867324666170426095015.
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.
14-3-3是一类能够通过建立蛋白质-蛋白质相互作用（PPI）与多种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且物种间序列同源性高。14-3-3蛋白通过触发或干扰特定蛋白质伴侣的活性，参与许多生理和病理细胞过程。在过去几年中，科学界收集了许多关于七种人类14-3-3同工型在癌症或神经退行性疾病中所起作用的证据。事实上，这些蛋白质通过与（i）致癌蛋白、（ii）促凋亡蛋白以及（iii）与帕金森病和阿尔茨海默病相关的蛋白质相互作用，调节与这些疾病相关的分子机制。14-3-3 PPI小分子调节剂的发现有助于全面了解这些蛋白质的生理作用，并可能为这些关键病理状态提供有价值的治疗方法。
