Abstract
The HECT-type E3 ligase Itch is increasingly being shown to have a vital role in immune regulation. Itch deficiency leads to deleterious inflammatory disorders both in mice and humans. By adding ubiquitin to the key signaling intermediates, Itch functions as a critical regulator of lymphocyte-cell activation, differentiation and immune tolerance. Also, Itch cooperates with deubiquitinating enzymes such as A20 and Cyld to terminate NF-κB signaling and prevent chronic inflammation. This review summarizes recent advances that highlight Itch's role in lymphocyte function and explores recent insights regarding its role as a regulator of inflammatory signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Differentiation / genetics
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DNA-Binding Proteins / metabolism
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Deubiquitinating Enzyme CYLD
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Humans
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Immunomodulation
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Inflammation / immunology*
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Intracellular Signaling Peptides and Proteins / metabolism
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Lymphocyte Activation / genetics
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Mice
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NF-kappa B / antagonists & inhibitors
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Nuclear Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction / genetics
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Tumor Necrosis Factor alpha-Induced Protein 3
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Tumor Suppressor Proteins / metabolism
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
Substances
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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Nuclear Proteins
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Repressor Proteins
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Tumor Suppressor Proteins
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ITCH protein, human
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Ubiquitin-Protein Ligases
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CYLD protein, human
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Deubiquitinating Enzyme CYLD
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TNFAIP3 protein, human
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Tumor Necrosis Factor alpha-Induced Protein 3