The NLRP1 and CARD8 inflammasomes

Author:

Taabazuing Cornelius Y.1,Griswold Andrew R.23,Bachovchin Daniel A.143ORCID

Affiliation:

1. Chemical Biology Program Memorial Sloan Kettering Cancer Center New York NY USA

2. Weill Cornell, Rockefeller, Sloan Kettering Tri‐Institutional MD‐PhD Program New York NY USA

3. Pharmacology Program of the Weill Cornell Graduate School of Medical Sciences Memorial Sloan Kettering Cancer Center New York NY USA

4. Tri‐Institutional PhD Program in Chemical Biology Memorial Sloan Kettering Cancer Center New York NY USA

Abstract

AbstractInflammasomes are multiprotein complexes that activate inflammatory cytokines and induce pyroptosis in response to intracellular danger‐associated signals. NLRP1 and CARD8 are related germline‐encoded pattern recognition receptors that form inflammasomes, but their activation mechanisms and biological purposes have not yet been fully established. Both NLRP1 and CARD8 undergo post‐translational autoproteolysis to generate two non‐covalently associated polypeptide chains. NLRP1 and CARD8 activators induce the proteasome‐mediated destruction of the N‐terminal fragment, liberating the C‐terminal fragment to form an inflammasome. Here, we review the danger‐associated stimuli that have been reported to activate NLRP1 and/or CARD8, including anthrax lethal toxin, Toxoplasma gondii, Shigella flexneri and the small molecule DPP8/9 inhibitor Val‐boroPro, focusing on recent mechanistic insights and highlighting unresolved questions. In addition, we discuss the recently identified disease‐associated mutations in NLRP1 and CARD8, the potential role that DPP9’s protein structure plays in inflammasome regulation, and the emerging link between NLRP1 and metabolism. Finally, we summarize all of this latest research and consider the possible biological purposes of these enigmatic inflammasomes.

Funder

Alfred P. Sloan Foundation

American Cancer Society

Gabrielle’s Angel Foundation for Cancer Research

Stand Up To Cancer

Pew Charitable Trusts

Publisher

Wiley

Cited by 147 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.7亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2025 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3