A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells has regulatory sequences within its gene
Year: 2018
Type: article
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.
Source: Journal of Biological Chemistry
Authors: Sunil Kaul, Sharad K. Mittal, Paul A. Roche
Institutions: National Institutes of Health, National Cancer Institute
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funder: National Cancer Institute
OpenAlex ID: W2787170337