Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
Department of Cellular and Molecular Medicine, Laboratory of Biosignaling & Therapeutics, Katholieke Universiteit Leuven, Louvain, Belgium.
Cell Commun Signal. 2024 Jan 24;22(1):65. doi: 10.1186/s12964-023-01468-8.
Protein Phosphatase 1 (PP1) is a major serine/threonine phosphatase in eukaryotes, participating in several cellular processes and metabolic pathways. Due to their low substrate specificity, PP1's catalytic subunits do not exist as free entities but instead bind to Regulatory Interactors of Protein Phosphatase One (RIPPO), which regulate PP1's substrate specificity and subcellular localization. Most RIPPOs bind to PP1 through combinations of short linear motifs (4-12 residues), forming highly specific PP1 holoenzymes. These PP1-binding motifs may, hence, represent attractive targets for the development of specific drugs that interfere with a subset of PP1 holoenzymes. Several viruses exploit the host cell protein (de)phosphorylation machinery to ensure efficient virus particle formation and propagation. While the role of many host cell kinases in viral life cycles has been extensively studied, the targeting of phosphatases by viral proteins has been studied in less detail. Here, we compile and review what is known concerning the role of PP1 in the context of viral infections and discuss how it may constitute a putative host-based target for the development of novel antiviral strategies.
蛋白磷酸酶 1(PP1)是真核生物中主要的丝氨酸/苏氨酸磷酸酶,参与多种细胞过程和代谢途径。由于其底物特异性低,PP1 的催化亚基不是以游离形式存在,而是与蛋白磷酸酶 1 的调节相互作用蛋白(RIPPO)结合,后者调节 PP1 的底物特异性和亚细胞定位。大多数 RIPPO 通过短线性基序(4-12 个残基)的组合与 PP1 结合,形成高度特异性的 PP1 全酶。因此,这些 PP1 结合基序可能代表开发特定药物的有吸引力的靶点,这些药物可以干扰一组特定的 PP1 全酶。一些病毒利用宿主细胞蛋白(去)磷酸化机制来确保病毒颗粒的有效形成和传播。虽然许多宿主细胞激酶在病毒生命周期中的作用已被广泛研究,但病毒蛋白对磷酸酶的靶向作用研究得较少。在这里,我们收集并回顾了已知的关于 PP1 在病毒感染背景下的作用,并讨论了它如何可能成为开发新型抗病毒策略的潜在基于宿主的靶标。