Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86

Liu, H; Wilson, KR; Firth, AM; Macri, C; Schriek, P; Blum, AB; Villar, J; Wormald, S; Shambrook, M; Xu, B; Lim, HJ; McWilliam, HEG; Hill, AF; Edgington-Mitchell, LE; Caminschi, I; Lahoud, MH; Segura, E; Herold, MJ; Villadangos, JA; Mintern, JD

Author(s): Liu, H; Wilson, KR; Firth, AM; Macri, C; Schriek, P; Blum, AB; Villar, J; Wormald, S; Shambrook, M; Xu, B; Lim, HJ; McWilliam, HEG; Hill, AF; Edgington-Mitchell, LE; Caminschi, I; Lahoud, MH; Segura, E; Herold, MJ; Villadangos, JA; Mintern, JD;
Details: Publication Year 2022-04-11,Volume 13,Issue #1,Page 1934
Journal Title: Nature Communications
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.
Publisher: NPG
Keywords: Animals; B7-2 Antigen/metabolism; Dendritic Cells; *Histocompatibility Antigens Class II/metabolism; Major Histocompatibility Complex; Mice; Mice, Inbred C57BL; Ubiquitin-Protein Ligases/metabolism; Ubiquitination; *Ubiquitins/metabolism
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 35411049
Publisher's Version: https://doi.org/10.1038/s41467-022-29524-w
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-022-29524-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.
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Creation Date: 2022-05-03 09:18:34

Last Modified: 2022-05-03 09:37:48