CTLA-4 (CD152) inhibits T cell function by activating the ubiquitin ligase Itch.
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.
Mesh Terms:
Animals, Antigens, CD, Blotting, Western, Enzyme Activation, Immunoprecipitation, Lymphocyte Activation, Mice, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Lymphocytes, Ubiquitin-Protein Ligases, Ubiquitination
Animals, Antigens, CD, Blotting, Western, Enzyme Activation, Immunoprecipitation, Lymphocyte Activation, Mice, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Lymphocytes, Ubiquitin-Protein Ligases, Ubiquitination
Mol. Immunol.
Date: Jun. 01, 2010
PubMed ID: 20417562
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