| Autor: |
Rajan Venkatraman, Katherine R. Balka, Wilson Wong, Jananipriya Sivamani, Zoe Magill, Kirsteen M. Tullett, Rachael M. Lane, Tahnee L. Saunders, Maximilien Tailler, Peter J. Crack, Linda M. Wakim, Mireille H. Lahoud, Kate E. Lawlor, Benjamin T. Kile, Meredith O’Keeffe, Dominic De Nardo |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 9, Pp 110693- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.110693 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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