Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA.
Cell Res. 2011 Jan;21(1):22-39. doi: 10.1038/cr.2010.166. Epub 2010 Nov 30.
Nuclear factor-kappa B (NF-κB) is a critical regulator of multiple biological functions including innate and adaptive immunity and cell survival. Activation of NF-κB is tightly regulated to preclude chronic signaling that may lead to persistent inflammation and cancer. Ubiquitination of key signaling molecules by E3 ubiquitin ligases has emerged as an important regulatory mechanism for NF-κB signaling. Deubiquitinases (DUBs) counteract E3 ligases and therefore play a prominent role in the downregulation of NF-κB signaling and homeostasis. Understanding the mechanisms of NF-κB downregulation by specific DUBs such as A20 and CYLD may provide therapeutic opportunities for the treatment of chronic inflammatory diseases and cancer.
核因子-κB（NF-κB）是调节多种生物学功能的关键因子，包括先天免疫和适应性免疫以及细胞存活。NF-κB 的激活受到严格调控，以防止可能导致持续炎症和癌症的慢性信号转导。E3 泛素连接酶对关键信号分子的泛素化已成为 NF-κB 信号转导的重要调节机制。去泛素化酶（DUBs）与 E3 连接酶拮抗，因此在 NF-κB 信号转导和动态平衡的下调中发挥重要作用。了解特定 DUB（如 A20 和 CYLD）下调 NF-κB 的机制可能为治疗慢性炎症性疾病和癌症提供治疗机会。
