title: Multifaceted role of the ubiquitin ligase Itch in immune regulation.
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.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.
authors.forename: K
authors.initials: K
authors.lastname: Venuprasad
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Wayne State University, Detroit, MI, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Baughan
authors.affiliation: Department of Laboratory Medicine, Lund University, Medicon Village, Lund, Sweden.
authors.forename: Ramin
authors.initials: R
authors.lastname: Massoumi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009687:Nuclear Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3