| First Author | Fei X | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112586 |
| PubMed ID | 37267109 | Mgi Jnum | J:341034 |
| Mgi Id | MGI:7491418 | Doi | 10.1016/j.celrep.2023.112586 |
| Citation | Fei X, et al. (2023) The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-kappaB. Cell Rep 42(6):112586 |
| abstractText | The nuclear factor kappaB (NF-kappaB) pathway plays essential roles in innate and adaptive immunity, but little is known how NF-kappaB 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-kappaB. SREBP cleavage-activating protein (Scap) and sterol regulatory element-binding protein 1 (SREBP1) form a super complex with inhibitors of NF-kappaB alpha (IkappaBalpha) to associate NF-kappaB 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 IkappaBalpha for IkappaB kinase (Ikk)-mediated phosphorylation and subsequent activation of NF-kappaB. Loss of Scap or inhibition of S1P or S2P diminishes, while SREBP1 deficiency augments, LPS-induced NF-kappaB activation and subsequent inflammatory responses. Our results reveal the Scap-SREBP1 complex as an additional cytoplasmic checkpoint for NF-kappaB homeostasis and unveil the Golgi apparatus as the optimal cellular platform for NF-kappaB activation, providing insights into the crosstalk between lipogenesis signaling and immunity. |
