ArticleCellular & molecular immunology2026
MARCH2/3 target FcγRI for K27-linked polyubiquitination and degradation to restrict the inflammatory response.
Article in Cellular & molecular immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
IgG Fc gamma receptor I (FcγRI) belongs to the immunoglobulin superfamily and plays a pivotal role in immune regulation. The post-translational regulation of FcγRI and its effects on immune regulation are unclear. In this study, we identified the membrane-associated RING-CH-type finger (MARCH) E3 ubiquitin ligases MARCH2 and MARCH3 as physiological regulators of FcγRI. MARCH2 and MARCH3 associate with FcγRI and mediate its K27-linked polyubiquitination at K336 and K368, respectively, leading to subsequent lysosomal degradation. While deficiency of either MARCH2 or MARCH3 modestly increases FcγRI levels as well as LPS- and IgG-induced transcription of downstream genes, double knockout of MARCH2/3 has a more dramatic effect. Double knockout of MARCH2/3 increases LPS-induced transcription of downstream genes in wild-type but not FcγRI knockout cells, and reconstitution of FcγRI
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