TANK结合激酶1在固有免疫应答中的作用及其泛素化调控

Biological functions and ubiquitin modification of TBK1 in innate immunity

摘要:

固有免疫系统通过模式识别受体识别病原微生物表面的病原相关分子模式启动固有免疫反应，经级联信号转导，激活下游转录因子NF-κB和干扰素调节因子IRFs，进而产生炎性细胞因子以及Ⅰ型干扰素，抵抗病原微生物感染。TANK结合激酶1 (TANK binding kinase 1，TBK1) 作为一个中心节点蛋白，参与多条固有免疫信号通路的传导，可同时激活NF-κB和IRFs，是机体抗感染过程中关键的蛋白激酶。TBK1的精准调控对维持机体免疫稳态、抵抗病原体入侵至关重要。文中综述了TBK1在固有免疫应答中的作用及其泛素化调控机制，以期为病原体感染及自身免疫病的临床治疗提供理论基础。

Abstract:

The innate immune system initiates innate immune responses by recognizing pathogen-related molecular patterns on the surface of pathogenic microorganisms through pattern recognition receptors. Through cascade signal transduction, it activates downstream transcription factors NF-κB and interferon regulatory factors (IRFs), and then leads to the production of inflammatory cytokines and type Ⅰ interferon, which resists the infection of pathogenic microorganism. TBK1 is a central adapter protein of innate immune signaling pathway and can activate both NF-κB and IRFs. It is a key protein kinase in the process of anti-infection. The finetuning regulation of TBK1 is essential to maintain immune homeostasis and resist pathogen invasion. This paper reviews the biological functions and ubiquitin modification of TBK1 in innate immunity, to provide theoretical basis for clinical treatment of pathogenic infections and autoimmune diseases.