Autoubiquitylation of the V(D)J recombinase protein RAG1
- Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5/Room 241, Bethesda, MD 20892
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Contributed by Martin Gellert, October 29, 2003
Abstract
V(D)J recombination, the rearrangement of gene segments to assemble Ig and T cell receptor coding regions, is vital to B and T lymphocyte development. Here, we demonstrate that the V(D)J recombinase protein RAG1 undergoes ubiquitylation in cells. In vitro, the RING finger domain of RAG1 acts as a ubiquitin ligase that mediates its own ubiquitylation at a highly conserved K residue in the RAG1 amino-terminal region. Ubiquitylation is best supported by a specific ubiquitin-conjugating enzyme, UbcH3/CDC34, and requires an intact RAG1 RING finger motif. Disruption of the RING finger and certain RAG1 N-terminal truncations are associated with immunodeficiency in human patients, suggesting that RAG1's ubiquitin ligase is required for its biological role in lymphocyte development.
Footnotes
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↵ † To whom correspondence should be addressed. E-mail: gellert{at}helix.nih.gov.
- Copyright © 2003, The National Academy of Sciences
