| First Author | Anandasabapathy N | Year | 2003 |
| Journal | Immunity | Volume | 18 |
| Issue | 4 | Pages | 535-47 |
| PubMed ID | 12705856 | Mgi Jnum | J:83012 |
| Mgi Id | MGI:2656456 | Doi | 10.1016/s1074-7613(03)00084-0 |
| Citation | Anandasabapathy N, et al. (2003) GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells. Immunity 18(4):535-47 |
| abstractText | T cell anergy may serve to limit autoreactive T cell responses. We examined early changes in gene expression after antigen-TCR signaling in the presence (activation) or absence (anergy) of B7 costimulation. Induced expression of GRAIL (gene related to anergy in lymphocytes) was observed in anergic CD4(+) T cells. GRAIL is a type I transmembrane protein that localizes to the endocytic pathway and bears homology to RING zinc-finger proteins. Ubiquitination studies in vitro support GRAIL function as an E3 ubiquitin ligase. Expression of GRAIL in retrovirally transduced T cell hybridomas dramatically limits activation-induced IL-2 and IL-4 production. Additional studies suggest that GRAIL E3 ubiquitin ligase activity and intact endocytic trafficking are critical for cytokine transcriptional regulation. Expression of GRAIL after an anergizing stimulus may result in ubiquitin-mediated regulation of proteins essential for mitogenic cytokine expression, thus positioning GRAIL as a key player in the induction of the anergic phenotype. |
