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bioRxiv · 10.1101/2023.06.21.545972

SCFFBXW11 complex targets interleukin-17 receptor A for ubiquitin-proteasome-mediated degradation.

Jin, B.·Moududee, S. A.·Ge, D.·Liu, Y.·Wang, A. R.·Zhou, P.·You, Z.
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Abstract

Interleukin-17 (IL-17) is a pro-inflammatory cytokine, participating in innate and adaptive immune responses, that plays an important role in host defense, autoimmune diseases, tissue regeneration, metabolic regulation, and tumor progression. Post-translational modifications (PTMs) are crucial for protein function, stability, cellular localization, cellular transduction, and cell death. However, PTMs of IL-17 receptor A (IL-17RA) have not been investigated. Here, we showed that human IL-17RA was targeted by F-box and WD repeats domain containing 11 (FBXW11) for ubiquitination, followed by proteasome-mediated degradation. We used bioinformatics tools and biochemical techniques to determine that FBXW11 ubiquitinated IL-17RA through a lysine 27-linked polyubiquitin chain, targeting IL-17RA for proteasomal degradation. Domain 665-804 of IL-17RA was critical for interaction with FBXW11 and subsequent ubiquitination. Our study demonstrates that FBXW11 regulates IL-17 signaling pathways at IL-17RA level.

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Jin, B., Moududee, S. A., Ge, D., Liu, Y., Wang, A. R., Zhou, P., You, Z.. 2023-06-22. SCFFBXW11 complex targets interleukin-17 receptor A for ubiquitin-proteasome-mediated degradation.. https://doi.org/10.1101/2023.06.21.545972

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