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.
(c) 2010 AACR.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Forkhead Transcription Factors / biosynthesis
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Humans
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Immune System
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Immune Tolerance*
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Mice
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Neoplasms / metabolism
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Proto-Oncogene Proteins c-cbl / metabolism*
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Repressor Proteins / metabolism*
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Signal Transduction
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T-Lymphocytes / cytology
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T-Lymphocytes / metabolism*
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T-Lymphocytes, Regulatory / cytology
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Transforming Growth Factor beta1 / metabolism
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Ubiquitin-Protein Ligases / metabolism*
Substances
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FOXP3 protein, human
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Forkhead Transcription Factors
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Repressor Proteins
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Transforming Growth Factor beta1
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ITCH protein, human
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Itch protein, mouse
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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CBL protein, human
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Cbl protein, mouse