Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity.
Engagement of the T cell receptor (TCR) with its cognate peptide/MHC initiates a cascade of signaling events that results in T cell activation. Limiting the extent and duration of TCR signaling ensures a tightly constrained response, protecting cells from the deleterious impact of chronic activation. In order to limit the duration of activation, T cells must adjust levels of key signaling proteins. This can be accomplished by altering protein synthesis or by changing the rate of protein degradation. Ubiquitination is a process of 'tagging' a protein with ubiquitin and is one means of initiating protein degradation. This process is activated when an E3 ubiquitin ligase mediates the transfer of ubiquitin to a target protein. Accordingly, E3 ubiquitin ligases have recently emerged as key regulators of immune cell function. This review will explore how a small group of E3 ubiquitin ligases regulate T cell responses and thus direct adaptive immunity.
Gay
Denise L
DL
The Children's Hospital of Philadelphia, Joseph Stokes, Jr. Research Institute, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Ramón
Hilda
H
Oliver
Paula M
PM
D000818:Animals; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007109:Immunity / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D000075702:Nedd4 Ubiquitin Protein Ligases; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D056827:Endosomal Sorting Complexes Required for Transport; C471637:Itch protein, mouse; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618461:Nedd4l protein, mouse; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases