AI Article Synopsis
- IL-17 plays a dual role in the immune system, offering protection against fungi and bacteria while also contributing to autoimmune diseases.
- Researchers used a new mass spectrometry technique to analyze the IL-17 receptor (IL-17R) complex and discovered the linear ubiquitin chain assembly complex (LUBAC) as a key signaling component.
- A crucial negative feedback loop involving the kinases TBK1 and IKKε was identified, which helps to terminate IL-17 signaling by modifying the adaptor ACT1 and releasing the ubiquitin ligase TRAF6, with NEMO having a unique role in negatively regulating this pathway.
Article Abstract
IL-17 mediates immune protection from fungi and bacteria, as well as it promotes autoimmune pathologies. However, the regulation of the signal transduction from the IL-17 receptor (IL-17R) remained elusive. We developed a novel mass spectrometry-based approach to identify components of the IL-17R complex followed by analysis of their roles using reverse genetics. Besides the identification of linear ubiquitin chain assembly complex (LUBAC) as an important signal transducing component of IL-17R, we established that IL-17 signaling is regulated by a robust negative feedback loop mediated by TBK1 and IKKε. These kinases terminate IL-17 signaling by phosphorylating the adaptor ACT1 leading to the release of the essential ubiquitin ligase TRAF6 from the complex. NEMO recruits both kinases to the IL-17R complex, documenting that NEMO has an unprecedented negative function in IL-17 signaling, distinct from its role in NF-κB activation. Our study provides a comprehensive view of the molecular events of the IL-17 signal transduction and its regulation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459424 | PMC |
| http://dx.doi.org/10.15252/embj.2019104202 | DOI Listing |
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