IndraLab

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"In line with this, previous work have identified a link between cholesterol homeostasis and STING activation in which the depletion of cholesterol could spontaneously activate STING, independent of li[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Given that cholesterol depletion promotes STING activation, we next explored whether ER cholesterol levels were generally reduced after cGAMP stimulation."

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"Collectively, these data support that ER cholesterol levels are reduced by SOAT1 at the early stages after cGAMP stimulation to support STING activation prior to the formation of STING oligomerization, phosphorylation, and recruitment of TBK1, which all occur after STING complexes have exited the ER compartment."

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"Together, these data support a mechanism by which cholesterol impairs STING-ER exit through a direct binding to STING CRAC motifs and thereby blocks STING trafficking, thus preventing activating of signaling."

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"We observed that cholesterol depletion significantly increased ER membrane positive curvature (Fig. 4a) and also caused the distribution of STING within the cells to increasingly expand along the ER membrane curvature (Supplementary Fig. 5)."

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"Therefore, we wanted to explore whether cholesterol depletion could enhance STING-dependent anti-tumor activity in vivo.We first evaluated if increased STING activation in murine dendritic cells supported better antigen capacity and activation, as we had already shown in human monocyte-derived dendritic cells (see Supplementary Fig. 3b)."

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"Collectively, these data suggest that cholesterol depletion within the TME can augment STING-dependent anti-tumor activity by increasing STING activation and synergize with checkpoint blockage therapy."

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"Yet another study discovered that cholesterol removal in various in vitro conditions disrupted STING activation ."

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"The reduction of ER cholesterol levels likely causes both change in the fluidity of the ER membrane, and de-anchoring of STING from the membrane."

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"Intracellular cholesterol depletion potentiates IFN signaling by increasing the responsiveness of the STING/TBK1 axis regulating the activation of IFN regulatory factor 3, a key transcription factor d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Cholesterol inhibits stimulator of interferon genes (STING)-dependent antitumor activity by disrupting STING signaling in monocyte-derived dendritic cells."

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"The decreased cholesterol flux can induce type I interferon response in a STING-dependent manner, which can be eliminated by adding free cholesterol (32), moreover, a recent study clarifies that cholesterol in the Golgi membrane is essential for the activation of STING (33)."

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"However recent work suggests that reduction of cholesterol biosynthesis directly drives the anti-viral response via the ER bound signalling protein STING rather than decreasing nutrient availability to the virus."

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"XREF_BIBR The authors reported that a reduced cholesterol pool size resulting from limited flux through the mevalonate pathway could spontaneously induce a type I IFN response in a stimulator of interferon genes (STING, TMEM173)-dependent fashion."

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"In contrast, researchers demonstrated that de novo cholesterol synthesis increased ER cholesterol levels, which inhibited the phosphorylation of tank-binding kinase (TBK) and the stimulator of the IFN gene (STING)."

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"This increased cholesterol sequesters STING in the endoplasmic reticulum, hindering its activation and downstream interferon signaling."

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"A previous study of macrophages showed that cholesterol biosynthesis inhibition spontaneously engaged STING activation, 8 and here we also found that cholesterol-deficient T cells had modestly upregul[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Consequently, depletion of intracellular cholesterol levels enhances STING pathway activation upon cGAMP stimulation."

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"Since ER cholesterol enrichment is dependent on de novo cholesterol synthesis, whereas LDLR mediated uptake distributes cholesterol throughout the cell, we hypothesized that DENV depends on de novo cholesterol synthesis to inhibit STING and TBK activation."

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"Cholesterol impairs STING activation."