Extended Data Fig. 4: SREBP2 primes STING signalling independently of cGAS or MAVS. | Nature

Extended Data Fig. 4: SREBP2 primes STING signalling independently of cGAS or MAVS.

From: Tonic prime-boost of STING signalling mediates Niemann–Pick disease type C

Extended Data Fig. 4

a, Immunoblot analysis of the SREBP2 and STING activation in Npc1WT MEFs that were treated with mock or triparanol (14 μM) for the indicated times (shown on the top). SREBP2 cleavage indicates activation. STING activation induces pSTING and pTBK1. b, Fluorescent microscopy analysis of SREBP2 and STING activation. Cleaved SREBP2 translocates to the nucleus (red). The STING activation markers pSTING, pTBK1 and pIRF3 are shown in green. The nucleus dye DAPI is shown in blue. Scale bars, 10 μm. c, qRT–PCR analysis of cholesterol-synthesis genes in BMDMs that were either mock-treated or treated with triparanol (14 μM) for 12 h (n = 3). d, qRT–PCR analysis of the baseline expression of ISGs in BMDMs that were either mock-treated or treated with triparanol (14 μM) alone or in combination with the STING inhibitor C-176 (0.5 μM) for 12 h (n = 3). e, f, qRT–PCR analysis of cholesterol-synthesis genes (e) and ISGs (f) in wild-type, Sting1−/− and Cgas−/− BMDMs that were either mock-treated or treated with triparanol (14 μM) for 12 h (n = 3). g, h, qRT–PCR analysis of the expression of cholesterol-synthesis genes (g) and ISGs (h) in Mavs−/− MEFs that were either mock-treated or treated with triparanol (14 μM) for 12 h (n = 3). i, j, qRT–PCR analysis of the cholesterol-synthesis gene Hmgcs1, knockdown efficiency of Insig1 (i) and the expression of ISGs (j) in wild-type, Cgas−/− and Sting1−/− MEFs (n = 3). cj, Data are mean ± s.d. Unpaired two-tailed Student’s t-test. Data are representative of at least two independent experiments.

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