Abstract:
:The active ubiquitin E3 ligase GRAIL is crucial in the induction of CD4 T cell anergy. Here we show that GRAIL is associated with and regulated by two isoforms of the ubiquitin-specific protease otubain 1. In lethally irradiated mice reconstituted with bone marrow cells from T cell receptor-transgenic mice retrovirally transduced to express the genes encoding these proteases, otubain 1-expressing cells contained negligible amounts of endogenous GRAIL, proliferated well and produced large amounts of interleukin 2 after antigenic stimulation. In contrast, cells expressing the alternatively spliced isoform, otubain 1 alternative reading frame 1, contained large amounts of endogenous GRAIL and were functionally anergic, and they proliferated poorly and produced undetectable interleukin 2 when stimulated in a similar way. Thus, these two proteins have opposing epistatic functions in controlling the stability of GRAIL expression and the resultant anergy phenotype in T cells.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Soares L,Seroogy C,Skrenta H,Anandasabapathy N,Lovelace P,Chung CD,Engleman E,Fathman CGdoi
10.1038/ni1017keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
45-54issue
1eissn
1529-2908issn
1529-2916pii
ni1017journal_volume
5pub_type
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