| First Author | Hoff H | Year | 2010 |
| Journal | Mol Immunol | Volume | 47 |
| Issue | 10 | Pages | 1875-81 |
| PubMed ID | 20417562 | Mgi Jnum | J:160620 |
| Mgi Id | MGI:4454731 | Doi | 10.1016/j.molimm.2010.03.017 |
| Citation | Hoff H, et al. (2010) CTLA-4 (CD152) inhibits T cell function by activating the ubiquitin ligase Itch. Mol Immunol 47(10):1875-81 |
| abstractText | CTLA-4 (CD152) is a regulatory molecule in the immune system fundamentally important for the inhibition of T cell activity that is mediated by an unknown mechanism. Here we demonstrate similarities of CTLA-4 and Itch deficient mice and that CTLA-4 deficient T cells show a massive reduction in the overall ubiquitination of proteins. CTLA-4-mediated signal transduction leads to increased de-phosphorylation and therefore activation of the ubiquitin ligase Itch and enhanced ubiquitination of the Itch target molecule JunB. The knock-down of Itch completely abolishes the inhibitory effect of CTLA-4-mediated signal transduction on mRNA accumulation of IFN-gamma and IL-4. These results show that CTLA-4 mediates signals via the activation of the ubiquitin ligase Itch probably leading to the enhanced ubiquitination of Itch target molecules resulting in inhibition of T cell activity. |
