Liao BW, Zhang HY, Du WT, Ran Y, Wang YY, Xu ZS

The proinflammatory cytokine IL-1? is a crucial mediator of inflammatory responses. IL-1?-induced signaling is finely regulated by various mechanisms, and its imbalance is involved in a variety of diseases. In this study, we identified FAM177A1, a protein of unknown function, as a negative regulator of IL-1?-induced signaling in human cells. ...

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Overexpression of FAM177A1 inhibited IL-1?-triggered activation of NF-?B and transcription of inflammatory genes, whereas knockdown of FAM177A1 showed the opposite effects. Mechanistically, FAM177A1 competitively bound to the E3 ubiquitin ligase TRAF6 and impaired its interaction with the E2-conjugating enzyme Ubc13; therefore, it inhibited TRAF6-mediated polyubiquitination and recruitment of downstream signaling molecules. These findings reveal a function of FAM177A1 and promote our understanding of the regulatory mechanisms of IL-1?-induced inflammatory responses.

Date: Nov. 19, 2021

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