Cutting Edge: TCR-induced NAB2 enhances T cell function by coactivating IL-2 transcription.
TCR engagement leads to the up-regulation of genetic programs that can both activate and inhibit T cell function. The early growth receptor (Egr) proteins Egr-2 and Egr-3 have recently been identified as TCR-induced negative regulators of T cell function. NAB2 (NGFI-A-binding protein 2) is both a coactivator and a corepressor of Egr-mediated transcription and has been implicated in regulating Schwann cell myelination. In this report we demonstrate that NAB2 is induced by TCR engagement and that its expression is enhanced by the presence of costimulation. The overexpression of NAB2 enhanced IL-2 production while small interfering RNA to NAB2 markedly inhibited IL-2 expression. Mechanistically, we demonstrate that NAB2 enhances IL-2 transcription by acting as a coactivator for Egr-1. Indeed, chromatin immunoprecipitation analysis reveals that NAB2 is recruited to the Egr-1 binding site of the IL-2 promoter. Taken together, our findings identify NAB2 as a novel coactivator of T cell function.
Collins
Samuel
S
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Wolfraim
Lawrence A
LA
Drake
Charles G
CG
Horton
Maureen R
MR
Powell
Jonathan D
JD
D000818:Animals; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014158:Transcription, Genetic
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D007376:Interleukin-2; C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins