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Ubiquitination of HLA ‐ DO by MARCH family E 3 ligases
Author(s) -
Jahnke Martin,
Trowsdale John,
Kelly Adrian P.
Publication year - 2013
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201243043
Subject(s) - endocytic cycle , ubiquitin , biology , microbiology and biotechnology , endocytosis , ubiquitin ligase , biochemistry , receptor , gene
HLA ‐ DO ( DO ) is a nonclassical MHC class II ( MHC II) molecule that negatively regulates the ability of HLA ‐ DM to catalyse the removal of invariant chain‐derived CLIP peptides from classical MHC II molecules. Here, we show that DO is posttranslationally modified by ubiquitination. The location of the modified lysine residue is shared with all classical MHC II beta chains, suggesting a conserved function. Three membrane‐associated RING ‐ CH ( MARCH 1, 8 and 9) family E 3 ligases that polyubiquitinate MHC II induce similar profiles of polyubiquitination on DO β. All three MARCH proteins also influenced trafficking of DO indirectly by a mechanism that required the DO β encoded di‐leucine and tyrosine‐based endocytosis motifs. This may be the result of MARCH ‐induced ubiquitination of components of the endocytic machinery. MARCH 9 was by far the most efficient at inducing intracellular redistribution of DO but did not target molecules for lysosomal degradation. The specificity of MARCH 9 for HLA ‐ DQ and HLA ‐ DO suggests a need for common regulation of these two MHC ‐encoded molecules.