NLRP2, an Inhibitor of the NF-κB Pathway, Is Transcriptionally Activated by NF-κB and Exhibits a Nonfunctional Allelic Variant

NF-κB 等位基因 生物 NFKB1型 遗传学 细胞生物学 基因 信号转导 转录因子
作者
Ana Fontalba,Olga Gutiérrez,José L. Fernández-Luna
出处
期刊:Journal of Immunology [American Association of Immunologists]
卷期号:179 (12): 8519-8524 被引量:74
标识
DOI:10.4049/jimmunol.179.12.8519
摘要

Abstract NLRP2 has been shown to inhibit the NF-κB signaling pathway, and thus may contribute to modulate the inflammatory response, where NF-κB plays a major role. In this study, we report that expression of NLRP2 is induced upon differentiation of CD34+ hemopoietic progenitors into granulocyte or monocyte/macrophages. We also found that NLRP2 was up-regulated following differentiation of mesenchymal stem cells toward adipocytes. Notably, stimulation of HEK293T cells with TNF-α or overexpression of the p65 subunit of NF-κB resulted in up-regulation of NLRP2 and the formation of NF-κB-NLRP2 promoter complexes. Moreover, ectopic expression of p65 but not of other transcriptional regulators induced transactivation of the NLRP2 promoter. Thus, NLRP2 may control NF-κB activation through a regulatory loop. Nucleotide changes within the NACHT domain of other NLRP proteins have been associated with hereditary fever syndromes and chronic inflammatory diseases. We identified five single nucleotide polymorphisms present in the NACHT domain of NLRP2 by sequencing genomic DNA from 319 healthy controls. The frequencies of the rare alleles varied between 0.2 and 10%. Of note, one of these variants, I352S was unable to block the transcriptional activity of NF-κB and the formation of NF-κB-DNA-binding complexes following stimulation with TNF-α. Overall, our findings provide molecular insight into the expression of NLRP2 by NF-κB and suggest that a polymorphism within the NACHT domain of NLRP2 may contribute to the amplification of inflammatory responses due to a reduction of inhibitory signals on the NF-κB pathway.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
WDD完成签到,获得积分10
1秒前
研友_8yPY0Z发布了新的文献求助10
3秒前
爱学习的婷完成签到 ,获得积分10
3秒前
11秒前
swimming关注了科研通微信公众号
12秒前
Ayanami发布了新的文献求助10
15秒前
术士发布了新的文献求助10
16秒前
wangrr完成签到,获得积分10
16秒前
Ayanami完成签到,获得积分10
20秒前
22秒前
25秒前
26秒前
28秒前
在水一方发布了新的文献求助10
31秒前
舒适的晓山完成签到 ,获得积分10
32秒前
陌上之心完成签到 ,获得积分10
33秒前
Ingrid_26发布了新的文献求助10
33秒前
CH发布了新的文献求助10
33秒前
Amy完成签到,获得积分10
34秒前
jessicazhong完成签到,获得积分10
35秒前
35秒前
在水一方完成签到,获得积分10
36秒前
bc应助皮毛柔软的猫采纳,获得30
37秒前
归尘应助皮毛柔软的猫采纳,获得10
37秒前
37秒前
wrr应助皮毛柔软的猫采纳,获得10
37秒前
38秒前
wltwb发布了新的文献求助10
42秒前
研友_8yPY0Z完成签到,获得积分10
45秒前
blue完成签到,获得积分10
46秒前
满意一曲完成签到,获得积分20
48秒前
Ava应助谨慎哈密瓜采纳,获得10
50秒前
满意一曲发布了新的文献求助10
51秒前
55秒前
非而者厚应助整齐的夏之采纳,获得10
56秒前
57秒前
欣喜水桃发布了新的文献求助10
59秒前
916发布了新的文献求助10
1分钟前
谨慎哈密瓜完成签到,获得积分10
1分钟前
领导范儿应助清仔采纳,获得10
1分钟前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
ISCN 2024 – An International System for Human Cytogenomic Nomenclature (2024) 3000
Continuum Thermodynamics and Material Modelling 2000
Encyclopedia of Geology (2nd Edition) 2000
105th Edition CRC Handbook of Chemistry and Physics 1600
Maneuvering of a Damaged Navy Combatant 650
the MD Anderson Surgical Oncology Manual, Seventh Edition 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3777369
求助须知:如何正确求助?哪些是违规求助? 3322759
关于积分的说明 10211549
捐赠科研通 3038120
什么是DOI,文献DOI怎么找? 1667117
邀请新用户注册赠送积分活动 797971
科研通“疑难数据库(出版商)”最低求助积分说明 758103