The role of E3 ligases in autoimmunity and the regulation of autoreactive T cells.
The ubiquitination of proteins by E3 ligases has become an important regulatory mechanism for a variety of immune functions, including the maintenance of self tolerance and suppression of autoreactive T cell development. This review highlights recent advances in our knowledge of the functions in this context of known and potential E3 ligases, including autoimmune regulator (AIRE), TNF receptor-associated factor 6 (TRAF6), Casitas B cell lymphoma b (Cbl-b), gene related to anergy in lymphocytes (GRAIL), Itch, and Roquin. We discuss how disruptions to these molecules may contribute to the loss of T cell homeostasis and the pathogenesis of autoimmunity. We also report on the implications of the potential coordinated actions of these molecules for T cell anergy and regulatory T cell (Treg) functions. The great diversity of E3 ligases and the growing list of cellular processes in which ubiquitination plays a role make for an exciting field of research. Findings emerging from these investigations may suggest ways to exploit the therapeutic potential of manipulating ubiquitination, particularly for autoimmune disorders.
Lin
Amy Erica
AE
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Mak
Tak W
TW
D000818:Animals; D001327:Autoimmune Diseases; D015551:Autoimmunity; D017635:Clonal Anergy; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D044767:Ubiquitin-Protein Ligases