清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Phosphorylation Meets Ubiquitination: The Control of NF-κB Activity

生物 IκB激酶 磷酸化 转录因子 泛素 泛素连接酶 F盒蛋白 细胞生物学 核定位序列 NFKB1型 亚细胞定位 促炎细胞因子 NF-κB 激酶 细胞质 信号转导 遗传学 炎症 基因 免疫学
作者
Michael Karin,Yinon Ben‐Neriah
出处
期刊:Annual Review of Immunology [Annual Reviews]
卷期号:18 (1): 621-663 被引量:4608
标识
DOI:10.1146/annurev.immunol.18.1.621
摘要

NF-kappaB (nuclear factor-kappaB) is a collective name for inducible dimeric transcription factors composed of members of the Rel family of DNA-binding proteins that recognize a common sequence motif. NF-kappaB is found in essentially all cell types and is involved in activation of an exceptionally large number of genes in response to infections, inflammation, and other stressful situations requiring rapid reprogramming of gene expression. NF-kappaB is normally sequestered in the cytoplasm of nonstimulated cells and consequently must be translocated into the nucleus to function. The subcellular location of NF-kappaB is controlled by a family of inhibitory proteins, IkappaBs, which bind NF-kappaB and mask its nuclear localization signal, thereby preventing nuclear uptake. Exposure of cells to a variety of extracellular stimuli leads to the rapid phosphorylation, ubiquitination, and ultimately proteolytic degradation of IkappaB, which frees NF-kappaB to translocate to the nucleus where it regulates gene transcription. NF-kappaB activation represents a paradigm for controlling the function of a regulatory protein via ubiquitination-dependent proteolysis, as an integral part of a phosphorylationbased signaling cascade. Recently, considerable progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1. The multisubunit IkappaB kinase (IKK) responsible for inducible IkappaB phosphorylation is the point of convergence for most NF-kappaB-activating stimuli. IKK contains two catalytic subunits, IKKalpha and IKKbeta, both of which are able to correctly phosphorylate IkappaB. Gene knockout studies have shed light on the very different physiological functions of IKKalpha and IKKbeta. After phosphorylation, the IKK phosphoacceptor sites on IkappaB serve as an essential part of a specific recognition site for E3RS(IkappaB/beta-TrCP), an SCF-type E3 ubiquitin ligase, thereby explaining how IKK controls IkappaB ubiquitination and degradation. A variety of other signaling events, including phosphorylation of NF-kappaB, hyperphosphorylation of IKK, induction of IkappaB synthesis, and the processing of NF-kappaB precursors, provide additional mechanisms that modulate the level and duration of NF-kappaB activity.
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
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
摇摇猪发布了新的文献求助10
2秒前
QiWei完成签到 ,获得积分10
9秒前
9秒前
scarlet完成签到 ,获得积分10
13秒前
kaisa发布了新的文献求助10
13秒前
山止川行完成签到 ,获得积分10
13秒前
稻子完成签到 ,获得积分10
15秒前
摇摇猪完成签到,获得积分10
23秒前
缓慢的半莲完成签到 ,获得积分10
25秒前
直率小蕊完成签到 ,获得积分10
27秒前
30秒前
飞云完成签到 ,获得积分10
31秒前
WILSON发布了新的文献求助10
34秒前
善学以致用应助WILSON采纳,获得10
39秒前
雷九万班完成签到 ,获得积分10
56秒前
老高完成签到,获得积分10
1分钟前
lucky完成签到 ,获得积分10
1分钟前
孙雷完成签到 ,获得积分10
1分钟前
1分钟前
疯度发布了新的文献求助10
1分钟前
刻苦的新烟完成签到 ,获得积分10
1分钟前
丘比特应助疯度采纳,获得10
1分钟前
hmhu发布了新的文献求助10
1分钟前
华仔应助kevindm采纳,获得10
1分钟前
aiyawy完成签到 ,获得积分10
1分钟前
疯度完成签到,获得积分10
1分钟前
简单发布了新的文献求助10
1分钟前
2分钟前
kevindm发布了新的文献求助10
2分钟前
huazhangchina完成签到 ,获得积分10
2分钟前
huangzsdy完成签到,获得积分10
2分钟前
kevindm完成签到,获得积分10
2分钟前
简单完成签到,获得积分20
2分钟前
温馨家园完成签到 ,获得积分10
2分钟前
lhb完成签到,获得积分10
2分钟前
Ru完成签到 ,获得积分10
2分钟前
Sunny完成签到 ,获得积分10
2分钟前
wait完成签到 ,获得积分10
3分钟前
潇潇完成签到 ,获得积分10
3分钟前
铁妹儿完成签到 ,获得积分10
3分钟前
高分求助中
A pan-cancer cuproptosis signature predicting immunotherapy response and prognosis 1500
Straight Talk about ADHD in Girls: How to Help Your Daughter Thrive 1100
Lorenz Luthi - The Regional Cold Wars in Europe, East Asia, and the Middle East Crucial Periods and Turning Points 1000
Models of Teaching(The 10th Edition,第10版!)《教学模式》(第10版!) 800
Full waveform acoustic data processing 500
More Activities for Teaching Positive Psychology A Guide for Instructors 330
The Chicago Manual of Style, 18th Edition 300
热门求助领域 (近24小时)
化学 医学 材料科学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 免疫学 细胞生物学 电极
热门帖子
关注 科研通微信公众号,转发送积分 2887826
求助须知:如何正确求助?哪些是违规求助? 2507906
关于积分的说明 6789567
捐赠科研通 2183623
什么是DOI,文献DOI怎么找? 1160861
版权声明 586630
科研通“疑难数据库(出版商)”最低求助积分说明 569371