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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Science immunology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41417924/ |
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Table of Contents:
- Human OCEL1 senses bacterial infection to unlock inflammatory responses. Li, Zhi Wang, Jing Du, Juan Li, Jun Song, Yanan Zhu, Junji Li, Ziyi Zhou, Wei Chen, Shiyun Yang, Lijie Feng, Maohui Cai, Xiaolian Stacey, Katryn J Xiao, Wuhan Humans Animals Mice Inflammation NF-kappa B Pseudomonas Infections Signal Transduction Pseudomonas aeruginosa Mice, Inbred C57BL HEK293 Cells Processes that control tissue inflammation are essential to restore homeostasis after infection. The transcription factor NF-κB plays a central role in coordinating inflammation, but the mechanisms that regulate NF-κB signaling are not fully understood. Here, we identify () as a negative regulator of NF-κB signaling. In the absence of infection, human OCEL1 bound to the LZ domain of NEMO (NF-κB essential modulator) and inhibited TRAF6-mediated K63-linked polyubiquitination, suppressing NF-κB signaling. During infection, OCEL1-mediated negative regulation of NF-κB signaling was impaired by FK506-binding protein bacterial peptidyl-prolyl cis/trans isomerases, which bound to OCEL1 in an amino-terminal palindromic proline-rich element (PPE) and promoted its degradation. Mice expressing a mutant version of the human PPE had dampened inflammation and increased susceptibility to infection. Thus, the PPE of human OCEL1 senses bacterial infection, and its degradation releases the suppression of NF-κB signaling and promotes inflammation.