2023 journal article

NF-KB activation enhances STING signaling by altering microtubule-mediated STING trafficking

CELL REPORTS, 42(3).

By: L. Zhang *, X. Wei*, Z. Wang*, P. Liu*, Y. Hou *, Y. Xu *, H. Su *, M. Koci n , H. Yin *, C. Zhang *

MeSH headings : Interferons; NF-kappa B / metabolism; Signal Transduction / genetics; Toll-Like Receptors; Membrane Proteins
TL;DR: It is demonstrated that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking and triggering a cascade-amplified interferon response and robust host antiviral defense. (via Semantic Scholar)
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Source: Web Of Science
Added: April 4, 2023

It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.