The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Attenuation of c GAS ‐ STING signaling is mediated by a p62/ SQSTM 1‐dependent autophagy pathway activated by TBK1
Open accessAbstract
Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING Here, we report that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes. Degradation of STING was impaired in p62-deficient cells, which responded with elevated IFN production to foreign DNA and DNA pathogens. In the absence of p62, STING failed to traffic to autophagy-associated vesicles. Thus, DNA sensing induces the cGAS-STING pathway to activate TBK1, which phosphorylates IRF3 to induce IFN expression, but also phosphorylates p62 to stimulate STING degradation and attenuation of the response.
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Cites
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Cited by
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Metadata
- Authors
- Prabakaran, T., Bodda, C., Krapp, C., Zhang, B., Christensen, M. H., Sun, C., Reinert, L., Cai, Y., Jensen, S. B., Skouboe, M. K., Nyengaard, J. R., Thompson, C. B., Lebbink, R. J., Sen, G. C., van Loo, G., Nielsen, R., Komatsu, M., Nejsum, L. N., Jakobsen, M. R., Gyrd‐Hansen, M., & Paludan, S. R.
- Venue
- The EMBO Journal
- Published
- 2018-03
- Volume
- 37
- Issue
- 8
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W2790226049
- Cited by
- 489
- References
- 66
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Prabakaran, T., Bodda, C., Krapp, C., Zhang, B., Christensen, M. H., Sun, C., Reinert, L., Cai, Y., Jensen, S. B., Skouboe, M. K., Nyengaard, J. R., Thompson, C. B., Lebbink, R. J., Sen, G. C., van Loo, G., Nielsen, R., Komatsu, M., Nejsum, L. N., Jakobsen, M. R., . . . Paludan, S. R. (2018). Attenuation of c GAS ‐ STING signaling is mediated by a p62/ SQSTM 1‐dependent autophagy pathway activated by TBK1. The EMBO Journal. https://doi.org/10.15252/embj.201797858
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
