TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy
TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy
复制标题
TRIM11 通过 p62 依赖性选择性自噬降解 AIM2，从而抑制 AIM2 炎症小体
DOI：
10.1016/j.celrep.2016.07.019
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发表时间：
2016-08-16
期刊：
影响因子：
8.8
通讯作者：
Cui, Jun
中科院分区：
文献类型：
--
作者：
Liu, Tao;Tang, Qin;Cui, Jun
AIM2炎性小体是一个关键的细胞质信号复合体，由双链DNA激活，导致促炎细胞因子如白细胞介素-1 β (IL-1 β)和IL-18成熟。AIM2炎性小体活性失调与人类炎性疾病和癌症有关，提示其活性必须受到严格调控。然而，控制AIM2水平和活性的精确分子机制仍然知之甚少。在这里，我们报道了TRIM11是AIM2炎性体的一个关键负调控因子。在DNA病毒感染后，TRIM11通过其PS结构域与AIM2结合，并在K458位点发生自泛素化，促进TRIM11与自噬货物受体p62之间的关联，通过选择性自噬介导AIM2降解。这些发现确定了TRIMs在AIM2炎性小体激活中的作用，其中TRIM11作为二级受体以p62依赖的方式将AIM2传递到自噬小体进行降解。
The AIM2 inflammasome is a key cytosolic signaling complex that is activated by double-stranded DNA, leading to the maturation of proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and IL-18. Dysregulated AIM2 inflammasome activity is associated with human inflammatory diseases and cancers, suggesting that its activity must be tightly regulated. However, the precise molecular mechanisms that control AIM2 levels and activity are still poorly understood. Here, we report tripartite motif 11 (TRIM11) as a key negative regulator of the AIM2 inflammasome. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS domain and undergoes auto-polyubiquitination at K458 to promote an association between TRIM11 and the autophagic cargo receptor p62 to mediate AIM2 degradation via selective autophagy. These findings identify a role for TRIMs in AIM2 inflammasome activation where TRIM11 acts as a secondary receptor to deliver AIM2 to the autophagosomes for degradation in a p62-dependent manner.