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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Roche, Paul A. Furuta, Kazuyuki Walseng, Even |
| Description | Author Affiliation: Furuta K ( Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.); |
| Abstract | As sentinels of the immune system, dendritic cells (DCs) continuously generate and turnover antigenic peptide-MHC class II complexes (pMHC-II). pMHC-II generation is a complex process that involves many well-characterized MHC-II biosynthetic intermediates; however, the mechanisms leading to MHC-II turnover/degradation are poorly understood. We now show that pMHC-II complexes undergoing clathrin-independent endocytosis from the DC surface are efficiently ubiquitinated by the E3 ubiquitin ligase March-I in early endosomes, whereas biosynthetically immature MHC-II-Invariant chain (Ii) complexes are not. The inability of MHC-II-Ii to serve as a March-I substrate is a consequence of Ii sorting motifs that divert the MHC-II-Ii complex away from March-I(+) early endosomes. When these sorting motifs are mutated, or when clathrin-mediated endocytosis is inhibited, MHC-II-Ii complexes internalize by using a clathrin-independent endocytosis pathway and are now ubiquitinated as efficiently as pMHC-II complexes. These data show that the selective ubiquitination of internalizing surface pMHC-II in March-I(+) early endosomes promotes degradation of 'old' pMHC-II and spares forms of MHC-II that have not yet loaded antigenic peptides or have not yet reached the DC surface. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Dendritic Cells Immunology Endosomes Metabolism Multiprotein Complexes Peptides Biotinylation Genes, MHC Class II Genetics HEK293 Cells HeLa Cells Immunoblotting Immunoprecipitation Lysosomes Proteolysis RNA, Small Interfering Ubiquitination Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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