Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Semin Cell Dev Biol. 2021 Jan;109:144-150. doi: 10.1016/j.semcdb.2020.07.001. Epub 2020 Jul 3.
The receptor-interacting protein kinases (RIPKs) are key regulators of inflammatory signalling and cell death pathways triggered by innate immune receptors, and RIPKs have emerged as promising therapeutic targets for treatment of immune-related disorders. RIPK2 mediates signalling responses initiated by the bacterial-sensing pattern recognition receptors nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2), which play a key role in regulation of intestinal immunity and inflammation. Modification of RIPK2 by non-degradative ubiquitin chains generated by the E3 ubiquitin ligase XIAP and other ligases govern NOD1/2 signalling. Recent advances suggest that the interaction between RIPK2 and XIAP is a druggable protein-protein interaction to modulate NOD1/2-dependent immune responses. Here, we discuss the mechanistic function of RIPK2 in immune signalling, its clinical relevance, and the on-going efforts to target RIPK2 in inflammatory bowel disease and beyond.
受体相互作用蛋白激酶（RIPKs）是先天免疫受体触发的炎症信号和细胞死亡途径的关键调节剂，并且 RIPKs 已成为治疗与免疫相关疾病的有前途的治疗靶点。RIPK2 介导由细菌感应模式识别受体核苷酸结合寡聚化结构域蛋白 1 和 2（NOD1/2）引发的信号反应，NOD1/2 在调节肠道免疫和炎症中发挥关键作用。E3 泛素连接酶 XIAP 和其他连接酶产生的非降解泛素链对 RIPK2 的修饰控制 NOD1/2 信号。最近的进展表明，RIPK2 与 XIAP 之间的相互作用是一种可成药的蛋白-蛋白相互作用，可调节 NOD1/2 依赖性免疫反应。在这里，我们讨论了 RIPK2 在免疫信号中的作用机制、其临床相关性，以及靶向 RIPK2 在炎症性肠病及其他疾病中的研究进展。
