FAM177A1 Inhibits IL-1 beta-InducedSignalingbyImpairingTRAF6x9f;Ubc13 Association

The proinflammatory cytokine IL-1bis a crucial mediator of inflammatory responses. IL-1bx9f;induced signaling is finely regulatedby various mechanisms, and its imbalance is involved in a variety of diseases. In this study, we identified FAM177A1, a protein ofunknown function, as a negative regulator of IL-1bx9f;induced signaling in human cells. Overexpression of FAM177A1 inhibitedIL-1bx9f;triggered activation of NF-kB and transcription of inflammatory genes, whereas knockdown of FAM177A1 showed theopposite effects. Mechanistically, FAM177A1 competitively bound to the E3 ubiquitin ligase TRAF6 and impaired its interactionwith the E2-conjugating enzyme Ubc13; therefore, it inhibited TRAF6-mediated polyubiquitination and recruitment ofdownstream signaling molecules. These findings reveal a function of FAM177A1 and promote our understanding of theregulatory mechanisms of IL-1bx9f;induced inflammatory responses.The Journal of Immunology, 2021, 207: 3090x9f;3097.