Regulation of Inflammasome Activation by p62-Dependent Selective Autophagy
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- 英文论文题名：Regulation of Inflammasome Activation by p62-Dependent Selective Autophagy
- 论文作者：Liu Tao ; Cui Jun
- 英文论文作者：Liu Tao ; Cui Jun ; Sun Yat-sen University
- 年：2016
- 作者机构：Sun Yat-sen University;
- 英文论文关键词：autophagy ; inflammasome ; TRIM11 ; protein degradation ; p62
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R392
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：269k
- 原文格式：D
- 会议级别：全国
摘要
Autophagy is an evolutionarily conserved catabolic process, which is critical in protection against injurious stimuli. Defect in the autophagy process has strong associations with a variety of human diseases. Recent studies show that autophagy can also regulate innate immune responses, including inflammation. Delineation of the crosstalk between autophagy and innate immune responses is now being greatly facilitated by the use of autophagy deficient cells and mice. It has been reported that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasome components. TRIM20 acts as a platform for autophagic proteins assembly, and targets to the inflammasome components, including NLRP3, NLRP1, and pro–caspase 1, for autophagic degradation.Recently we use overexpression, RNAi, and knockout systems to demonstrate that TRIM11 suppresses AIM2 inflammasome activation by promoting the degradation of AIM2. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS domain. In the meantime, TRIM11 undergoes auto-polyubiquitination on its Lysine(K) 458 through its own E3 ligase activity to promote interactions between TRIM11 and the autophagic cargo receptor p62, to assist with the delivery of AIM2 aggregates to autophagosomes for degradation. These findings identify a previously unrecognized role of autophagy in inflammasome activation and provide insights into the mechanisms by which TRIM11 acts as a secondary receptor to assist AIM2 delivery to autophagosomes for degradation in a p62-dependent manner.
Autophagy is an evolutionarily conserved catabolic process, which is critical in protection against injurious stimuli. Defect in the autophagy process has strong associations with a variety of human diseases. Recent studies show that autophagy can also regulate innate immune responses, including inflammation. Delineation of the crosstalk between autophagy and innate immune responses is now being greatly facilitated by the use of autophagy deficient cells and mice. It has been reported that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasome components. TRIM20 acts as a platform for autophagic proteins assembly, and targets to the inflammasome components, including NLRP3, NLRP1, and pro–caspase 1, for autophagic degradation.Recently we use overexpression, RNAi, and knockout systems to demonstrate that TRIM11 suppresses AIM2 inflammasome activation by promoting the degradation of AIM2. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS domain. In the meantime, TRIM11 undergoes auto-polyubiquitination on its Lysine(K) 458 through its own E3 ligase activity to promote interactions between TRIM11 and the autophagic cargo receptor p62, to assist with the delivery of AIM2 aggregates to autophagosomes for degradation. These findings identify a previously unrecognized role of autophagy in inflammasome activation and provide insights into the mechanisms by which TRIM11 acts as a secondary receptor to assist AIM2 delivery to autophagosomes for degradation in a p62-dependent manner.
Autophagy is an evolutionarily conserved catabolic process, which is critical in protection against injurious stimuli. Defect in the autophagy process has strong associations with a variety of human diseases. Recent studies show that autophagy can also regulate innate immune responses, including inflammation. Delineation of the crosstalk between autophagy and innate immune responses is now being greatly facilitated by the use of autophagy deficient cells and mice. It has been reported that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasome components. TRIM20 acts as a platform for autophagic proteins assembly, and targets to the inflammasome components, including NLRP3, NLRP1, and pro–caspase 1, for autophagic degradation.Recently we use overexpression, RNAi, and knockout systems to demonstrate that TRIM11 suppresses AIM2 inflammasome activation by promoting the degradation of AIM2. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS domain. In the meantime, TRIM11 undergoes auto-polyubiquitination on its Lysine(K) 458 through its own E3 ligase activity to promote interactions between TRIM11 and the autophagic cargo receptor p62, to assist with the delivery of AIM2 aggregates to autophagosomes for degradation. These findings identify a previously unrecognized role of autophagy in inflammasome activation and provide insights into the mechanisms by which TRIM11 acts as a secondary receptor to assist AIM2 delivery to autophagosomes for degradation in a p62-dependent manner.
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