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Review
. 2010 Apr 15;70(8):3009-12.
doi: 10.1158/0008-5472.CAN-09-4076.

Cbl-b and itch: key regulators of peripheral T-cell tolerance

K Venuprasad  1
Affiliations
Review

Cbl-b and itch: key regulators of peripheral T-cell tolerance

K Venuprasad. Cancer Res. .

Abstract

E3 ligases Cbl-b and Itch have emerged as dominant "tolerogenic" regulators of T cells because their deficiency results in severe autoimmune diseases. Cbl-b and Itch ligase activity regulate T-cell anergy and development of Foxp3+ regulatory T cells (Treg) in the periphery by modulating key components of T-cell receptor (TCR) and transforming growth factor-beta (TGF-beta) signaling. Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer.

Keywords: Foxp3; Tolerance; Tregs; Ubiquitination; tumor Immunity.

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Figures

Figure 1
Figure 1
Cbl-b and Itch mediated regulation of TGF-β signaling and Foxp3 expression. Ligation of TCR in the presence of TGF-β results in phosphorylation of Smad2/3. Phosphorylated Smad2/3 in association with Smad4 translocates to the nucleus and induces Foxp3 transcription. Cbl-b regulates Foxp3 expression by modulating Smad2 phosphorylation. Itch targets TIEG1 for monoubiquitination which results in TIEG1 nuclear translocation and Foxp3 expression.
See this image and copyright information in PMC

References

    1. Walker LS, Abbas AK. The enemy within: keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol. 2002;2:11–9. - PubMed
    1. Venuprasad K, Yang C, Shao Y, et al. Immune regulation by ubiquitin conjugation. Adv Exp Med Biol. 2006;584:207–17. - PubMed
    1. Gao M, Karin M. Regulating the regulators: control of protein ubiquitination and ubiquitin-like modifications by extracellular stimuli. Mol Cell. 2005;19:581–93. - PubMed
    1. Chiang YJ, Kole HK, Brown K, et al. Cbl-b regulates the CD28 dependence of T-cell activation. Nature. 2000;403:216–20. - PubMed
    1. Bachmaier K, Krawczyk C, Kozieradzki I, et al. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature. 2000;403:211–6. - PubMed

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