The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-κB
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 6 vom: 27. Juni, Seite 112586 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fei, Xia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.10.2023 Date Revised 12.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112586 |
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| Förderinstitution / Projekttitel: |
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NLM357691458 |
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| 100 | 1 | |a Fei, Xia |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-κB |
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| 500 | |a Date Revised 12.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a metabolism | |
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| 700 | 1 | |a Huang, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuejue |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Zhehua |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Lingling |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yinfang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Boran |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Baihui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Weng, Qingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Kaijun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Shiyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Ying, Songmin |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Qiming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhihua |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Huahao |e verfasserin |4 aut | |
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