| First Author | Kaul S | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 12 | Pages | 4478-4485 |
| PubMed ID | 29378848 | Mgi Jnum | J:262767 |
| Mgi Id | MGI:6157212 | Doi | 10.1074/jbc.RA118.001775 |
| Citation | Kaul S, et al. (2018) A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells has regulatory sequences within its gene. J Biol Chem 293(12):4478-4485 |
| abstractText | 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. |
