Egr-2 and Egr-3 are negative regulators of T cell activation.
T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth response gene 2 (Egr-2) and Egr-3 as key negative regulators of T cell activation. Overexpression of Egr2 and Egr3 was associated with an increase in the E3 ubiquitin ligase Cbl-b and inhibition of T cell activation. Conversely, T cells from Egr3(-/-) mice had lower expression of Cbl-b and were resistant to in vivo peptide-induced tolerance. These data support the idea that Egr-2 and Egr-3 are involved in promoting a T cell receptor-induced negative regulatory genetic program.
Safford
Meredith
M
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Collins
Samuel
S
Lutz
Michael A
MA
Allen
Amy
A
Huang
Ching-Tai
CT
Kowalski
Jeanne
J
Blackford
Amanda
A
Horton
Maureen R
MR
Drake
Charles
C
Schwartz
Ronald H
RH
Powell
Jonathan D
JD
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051767:Early Growth Response Protein 2; D051776:Early Growth Response Protein 3; D015870:Gene Expression; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D050721:Proto-Oncogene Proteins c-cbl; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C497369:Egr3 protein, mouse; D014157:Transcription Factors; D051776:Early Growth Response Protein 3; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases