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• W2787170337 abstract "Regulation of major histocompatibility complex class II (MHC-II) expression is important not only to maintain a diverse pool of MHC-II–peptide complexes but also to prevent development of autoimmunity. The membrane-associated RING-CH (March) E3 ubiquitin ligase March-I regulates ubiquitination and turnover of MHC-II–peptide complexes in resting dendritic cells (DCs) and B cells. However, activation of either cell type terminates March-I expression, thereby stabilizing MHC-II–peptide complexes. Despite March-I’s important role in the biology of antigen-presenting cells (APCs), how expression of March-I mRNA is regulated remains unknown. We now show that both DCs and B cells possess a distinct isoform of March-I whose expression is regulated by a promoter located within the March-I gene. Using March-I promoter fragments to drive expression of GFP, we also identified a core promoter for expression of March-I in DCs and B cells, but not in fibroblasts, kidney cells, or epithelial cells, that contains regulatory regions that down-regulate March-I expression upon activation of DCs. Curiously, we found downstream sequence elements, present in the first coding exon of March-I in APCs, that confer regulation of March-I expression in activated APCs. In summary, our study identifies regulatory regions of the March-I gene that confer APC-specific expression and activation-induced modulation of March-I expression in DCs and B cells. Regulation of major histocompatibility complex class II (MHC-II) expression is important not only to maintain a diverse pool of MHC-II–peptide complexes but also to prevent development of autoimmunity. The membrane-associated RING-CH (March) E3 ubiquitin ligase March-I regulates ubiquitination and turnover of MHC-II–peptide complexes in resting dendritic cells (DCs) and B cells. However, activation of either cell type terminates March-I expression, thereby stabilizing MHC-II–peptide complexes. Despite March-I’s important role in the biology of antigen-presenting cells (APCs), how expression of March-I mRNA is regulated remains unknown. We now show that both DCs and B cells possess a distinct isoform of March-I whose expression is regulated by a promoter located within the March-I gene. Using March-I promoter fragments to drive expression of GFP, we also identified a core promoter for expression of March-I in DCs and B cells, but not in fibroblasts, kidney cells, or epithelial cells, that contains regulatory regions that down-regulate March-I expression upon activation of DCs. Curiously, we found downstream sequence elements, present in the first coding exon of March-I in APCs, that confer regulation of March-I expression in activated APCs. In summary, our study identifies regulatory regions of the March-I gene that confer APC-specific expression and activation-induced modulation of March-I expression in DCs and B cells." @default.
• W2787170337 created "2018-02-23" @default.
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• W2787170337 date "2018-03-01" @default.
• W2787170337 modified "2023-09-26" @default.
• W2787170337 title "A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells has regulatory sequences within its gene" @default.
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• W2787170337 doi "https://doi.org/10.1074/jbc.ra118.001775" @default.
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