The human pathogen Helicobacter pylori represents a risk factor for the development of gastric diseases including cancer. The H. pylori-induced transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is involved in the pro-inflammatory response and cell survival in the gastric mucosa, and represents a trailblazer of gastric pathophysiology. Termination of nuclear NF-κB heterodimer RelA/p50 activity is regulated by the ubiquitin-RING-ligase complex elongin-cullin-suppressor of cytokine signalling 1 (ECS^SOCS1), which leads to K48-ubiquitinylation and degradation of RelA. We found that deubiquitinylase (DUB) ubiquitin specific protease 48 (USP48), which interacts with the COP9 signalosome (CSN) subunit CSN1, stabilises RelA by deubiquitinylation and thereby promotes the transcriptional activity of RelA to prolong de novo synthesis of DUB A20 in H. pylori infection. An important role of A20 is the suppression of caspase-8 activity and apoptotic cell death. USP48 thus enhances the activity of A20 to reduce apoptotic cell death in cells infected with H. pylori. Our results, therefore, define a synergistic mechanism by which USP48 and A20 regulate RelA and apoptotic cell death in H. pylori infection.

人类病原体幽门螺杆菌代表了包括癌症在内的胃病发展的风险因素。H. pylori诱导的活化 B 细胞 (NF-κB)的转录因子核因子核因子 kappa-轻链增强子参与胃粘膜中的促炎反应和细胞存活，是胃病理生理学的先驱。核 NF-κB 异二聚体 RelA/p50 活性的终止受细胞因子信号传导 1 的泛素-环连接酶复合物细长蛋白-卡林抑制因子（ECS ^SOCS1)，这导致 RelA 的 K48 泛素化和降解。我们发现去泛素化酶 (DUB) 泛素特异性蛋白酶 48 (USP48) 与 COP9 信号体 (CSN) 亚基 CSN1 相互作用，通过去泛素化稳定 RelA，从而促进 RelA 的转录活性以延长H.幽门螺杆菌感染。A20 的一个重要作用是抑制 caspase-8 活性和凋亡细胞死亡。因此，USP48 增强了 A20 的活性，以减少感染幽门螺杆菌的细胞中的凋亡细胞死亡。因此，我们的结果定义了一种协同机制，USP48 和 A20 通过该机制调节幽门螺杆菌感染中的 RelA 和凋亡细胞死亡。