biostudies-literatureMallampalli RKBLRD VANHLBI NIH HHS5247-55https://www.ebi.ac.uk/biostudies/studies/S-EPMC3845358biostudies-literatureUnknown191(10)Cytokine-driven inflammation underlies the pathobiology of a wide array of infectious and immune-related disorders. The TNFR-associated factor (TRAF) proteins have a vital role in innate immunity by conveying signals from cell surface receptors to elicit transcriptional activation of genes encoding proinflammatory cytokines. We discovered that a ubiquitin E3 ligase F box component, termed Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by mediating the degradation of the TRAF inhibitory protein, Fbxl2. Analysis of the Fbxo3 C-terminal structure revealed that the bacterial-like ApaG molecular signature was indispensible for mediating Fbxl2 disposal and stimulating cytokine secretion. By targeting this ApaG motif, we developed a highly unique, selective genus of sJournal of immunology (Baltimore, Md. : 1950)Targeting F box protein Fbxo3 to control cytokine-driven inflammation.PMC3845358I01 BX002200R01 HL112791R01 HL116472R01 HL098174R01 HL097376R01 HL01916R01 HL096376Dunn SRGlasser JRWang CCoon TAChen BBWeathington NMZou CMallampalli RKZhao JZhao YfalseTargeting F box protein Fbxo3 to control cytokine-driven inflammation.Cytokine-driven inflammation underlies the pathobiology of a wide array of infectious and immune-related disorders. The TNFR-associated factor (TRAF) proteins have a vital role in innate immunity by conveying signals from cell surface receptors to elicit transcriptional activation of genes encoding proinflammatory cytokines. We discovered that a ubiquitin E3 ligase F box component, termed Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by mediating the degradation of the TRAF inhibitory protein, Fbxl2. Analysis of the Fbxo3 C-terminal structure revealed that the bacterial-like ApaG molecular signature was indispensible for mediating Fbxl2 disposal and stimulating cytokine secretion. By targeting this ApaG motif, we developed a highly unique, selective genus of s2013-01-01T00:00:00Z2013 Nov2025-04-04T12:27:01.284Z2019-03-26T23:43:01ZS-EPMC38453582412367810.4049/jimmunol.1300456