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• W4223422446 abstract "Abstract The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3 -deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses." @default.
• W4223422446 created "2022-04-14" @default.
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• W4223422446 date "2022-04-11" @default.
• W4223422446 modified "2023-10-18" @default.
• W4223422446 title "Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86" @default.
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• W4223422446 doi "https://doi.org/10.1038/s41467-022-29524-w" @default.
• W4223422446 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35411049" @default.
• W4223422446 hasPublicationYear "2022" @default.
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