IKKɛ induces STING non-IFN immune responses via a mechanism analogous to TBK1
- Author(s)
- Venkatraman, R; Balka, KR; Wong, W; Sivamani, J; Magill, Z; Tullett, KM; Lane, RM; Saunders, TL; Tailler, M; Crack, PJ; Wakim, LM; Lahoud, MH; Lawlor, KE; Kile, BT; O'Keeffe, M; De Nardo, D;
- Details
- Publication Year 2024-09-20,Volume 27,Issue #9,Page 110693
- Journal Title
- iScience
- Abstract
- The cGAS-STING pathway responds to cytosolic DNA to elicit host immunity to infection. The activation of stimulator of interferon genes (STING) can trigger a number of critical cellular responses including inflammation, noncanonical autophagy, lipid metabolism, senescence, and cell death. STING-mediated immunity through the production of type I interferons (IFNs) and nuclear factor kappa B (NF-κB)-driven proinflammatory cytokines is primarily driven via the effector protein TBK1. We have previously found that IκBα kinase epsilon (IKKε), a homolog of TBK1, can also facilitate STING-NF-κB responses. Therefore, a thorough understanding of how IKKε participates in STING signaling is essential. Here, we used a combination of genetic and biochemical approaches to provide mechanistic details into how IKKε confers non-IFN (e.g., NF-κB and MAPK) STING responses in macrophages, including in the absence of TBK1. We demonstrate a conserved mechanism of STING binding between TBK1 and IKKε. These findings strengthen our understanding of cGAS-STING signaling and the preservation of host immunity in cases of TBK1-deficiency.
- Publisher
- Elsevier
- Keywords
- Cell biology; Immunology; Molecular biology
- Research Division(s)
- Ubiquitin Signalling
- PubMed ID
- 39262777
- Publisher's Version
- https://doi.org/10.1016/j.isci.2024.110693
- Open Access at Publisher's Site
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Creation Date: 2024-10-04 10:45:18
Last Modified: 2024-10-04 10:51:24