Leicester Institute of Structural and Chemical Biology, University of Leicester, University Road, Leicester, LE1 7RH, UK; School of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK.
School of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK.
Curr Opin Struct Biol. 2024 Jun;86:102822. doi: 10.1016/j.sbi.2024.102822. Epub 2024 Apr 28.
Protein-protein interactions (PPIs) play a critical role in cellular signaling and represent interesting targets for therapeutic intervention. 14-3-3 proteins integrate many signaling targets via PPIs and are frequently implicated in disease, making them intriguing drug targets. Here, we review the recent advances in the 14-3-3 field. It will discuss the roles 14-3-3 proteins play within the cell, elucidation of their expansive interactome, and the complex mechanisms that underpin their function. In addition, the review will discuss significant advances in the development of molecular glues that target 14-3-3 PPIs. In particular, it will focus on novel drug discovery and development methodologies that have delivered selective, potent, and drug-like molecules that could open new avenues for the development of precision molecular tools and medicines.
蛋白质-蛋白质相互作用（PPIs）在细胞信号转导中起着关键作用，是治疗干预的有趣靶点。14-3-3 蛋白通过 PPIs 整合许多信号靶标，并且经常与疾病有关，因此它们是有趣的药物靶点。在这里，我们回顾了 14-3-3 领域的最新进展。它将讨论 14-3-3 蛋白在细胞内的作用、阐明其广泛的相互作用组以及支撑其功能的复杂机制。此外，该综述还将讨论靶向 14-3-3 PPI 的分子胶的重要进展。特别是，它将侧重于新的药物发现和开发方法，这些方法提供了选择性、高效和类药性的分子，为开发精确的分子工具和药物开辟了新的途径。
