甾醇调节元件结合蛋白
细胞生物学
脂肪生成
串扰
内质网
信号转导
高尔基体
磷酸化
NF-κB
IκB激酶
转录因子
先天免疫系统
生物
化学
生物化学
受体
脂质代谢
基因
物理
光学
作者
Fei Xia,Jiaqi Huang,Fĕi Li,Y. X. Wang,Zhehua Shao,Lingling Dong,Yangjie Wu,Boran Li,Xue Zhao,Bin Lv,Yun Zhao,Qingyu Weng,Kaijun Chen,Min Zhang,Shiyi Yang,Chao Zhang,Min Zhang,Wen Li,Songmin Ying,Qiming Sun,Zhihua Chen,Huahao Shen
出处
期刊:Cell Reports
[Elsevier]
日期:2023-06-01
卷期号:42 (6): 112586-112586
标识
DOI:10.1016/j.celrep.2023.112586
摘要
The nuclear factor κB (NF-κB) pathway plays essential roles in innate and adaptive immunity, but little is known how NF-κB signaling is compartmentalized and spatiotemporally activated in the cytoplasm. Here, we show that the lipogenesis signal cascade Scap-SREBP1-S1P/S2P orchestrates the homeostasis and spatiotemporal activation of NF-κB. SREBP cleavage-activating protein (Scap) and sterol regulatory element-binding protein 1 (SREBP1) form a super complex with inhibitors of NF-κB α (IκBα) to associate NF-κB close to the endoplasmic reticulum (ER). Upon lipopolysaccharide (LPS) stimulation, Scap transports the complex to the Golgi apparatus, where SREBP1 is cleaved by site-1 protease (S1P)/S2P, liberating IκBα for IκB kinase (Ikk)-mediated phosphorylation and subsequent activation of NF-κB. Loss of Scap or inhibition of S1P or S2P diminishes, while SREBP1 deficiency augments, LPS-induced NF-κB activation and subsequent inflammatory responses. Our results reveal the Scap-SREBP1 complex as an additional cytoplasmic checkpoint for NF-κB homeostasis and unveil the Golgi apparatus as the optimal cellular platform for NF-κB activation, providing insights into the crosstalk between lipogenesis signaling and immunity.
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