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Significance Infection of pathogenic microbes induces the body to produce cytokines, which are mediators of inflammation. IL-1β plays central roles in the initiation of inflammatory and immune responses. In this study, we identified MARCH3 protein, which negatively regulates IL-1β–triggered signaling and inflammatory response by mediating K48-linked polyubiquitination of IL-1RI at lysine 409 and its lysosomal degradation. Our findings reveal a mechanism for how IL-1β–triggered inflammatory response is attenuated by down-regulation of IL-1β receptor.

MARCH3 attenuates IL-1β–triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI