Genomes and Genes
Gene Symbol: Itch
Description: itchy, E3 ubiquitin protein ligase
Alias: 6720481N21Rik, 8030492O04Rik, A130065M08, AIP4, C230047C07Rik, E3 ubiquitin-protein ligase Itchy
- Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteinsVigo Heissmeyer
Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Nat Immunol 5:255-65. 2004..Calcineurin increased mRNA and protein of the E3 ubiquitin ligases Itch, Cbl-b and GRAIL and induced expression of Tsg101, the ubiquitin-binding component of the ESCRT-1 endosomal sorting ..
- Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated tyrosine phosphorylationChun Yang
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92130, USA
Mol Cell 21:135-41. 2006..mechanism involves regulation of the E3 Ub ligase, for example, the JNK-dependent phosphorylation and activation of Itch E3 ligase, which controls the turnover of Jun proteins and T cell differentiation...
- The ubiquitin-protein ligase Itch regulates p73 stabilityMario Rossi
Department of Biology, University of Rome Tor Vergata, Rome, Italy
EMBO J 24:836-48. 2005..However, unlike p53, p73 binds to, but is not degraded by, MDM2. Here we describe the binding of p73 to Itch, a Hect ubiquitin-protein ligase...
- The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnoverLufen Chang
Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute at City of Hope, City of Hope National Medical Center, 1500 E Duarte Road, KCRB 3009, Duarte, CA 91010, USA
Cell 124:601-13. 2006..direct c-FLIP phosphorylation but depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation...
- Convergence of Itch-induced ubiquitination with MEKK1-JNK signaling in Th2 tolerance and airway inflammationK Venuprasad
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
J Clin Invest 116:1117-26. 2006..containing a mitogen and extracellular kinase kinase 1 (MEKK1) mutant or lacking JNK1 or the E3 ubiquitin ligase Itch cannot be tolerized...
- Cbl-b and itch: key regulators of peripheral T-cell toleranceK Venuprasad
Department of Immunology and Microbiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Cancer Res 70:3009-12. 2010E3 ligases Cbl-b and Itch have emerged as dominant "tolerogenic" regulators of T cells because their deficiency results in severe autoimmune diseases...
- Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiationDeyu Fang
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
Nat Immunol 3:281-7. 2002b>Itch is an E3 ubiquitin ligase that is disrupted in nonagouti-lethal or itchy mice. Itch deficiency leads to severe immune and inflammatory disorders and constant itching of the skin...
- The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1K Venuprasad
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA
Nat Immunol 9:245-53. 2008..However, the molecular mechanisms leading to Foxp3 induction remain unclear. Here we show that Itch-/- T cells were resistant to TGF-beta treatment and had less Foxp3 expression...
- Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligaseL Qiu
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
J Biol Chem 275:35734-7. 2000Genetic studies identified Itch, which is a homologous to the E6-associated protein carboxyl terminus (Hect) domain-containing E3 ubiquitin-protein ligase that is disrupted in non-agouti lethal mice or Itchy mice...
- The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H miceW L Perry
Mammalian Genetics Laboratory, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Maryland 21702 1201, USA
Nat Genet 18:143-6. 1998..affects two loci: agouti and another, as yet unidentified locus designated itchy (the provisional gene symbol is Itch), that is responsible for the immunological phenotype of a18H mice...
- Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase ItchMin Gao
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Science 306:271-5. 2004..protein kinase cascade after T cell stimulation accelerated degradation of c-Jun and JunB through phosphorylation-dependent activation of the E3 ligase Itch. This pathway modulates cytokine production by effector T cells.
- Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activationToshiharu Sakurai
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California at San Diego, 9500 Gilman Drive MC 0723, La Jolla, CA 92093 0723, USA
Proc Natl Acad Sci U S A 103:10544-51. 2006....
- The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase ItchAndrew Oberst
Biochemistry Laboratory, Istituto Dermopatico dell Immacolata Istituto di Ricovero e Cura a Carattere Scientifico, University of Rome Tor Vergata, 00133 Rome, Italy
Proc Natl Acad Sci U S A 104:11280-5. 2007..Here, we describe a previously unrecognized functional interaction between N4BP1 and Itch, a Nedd4 structurally related E3, which contains four WW domains, conferring substrate-binding activity...
- The kinase IKKα inhibits activation of the transcription factor NF-κB by phosphorylating the regulatory molecule TAX1BP1Noula Shembade
Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, Florida, USA
Nat Immunol 12:834-43. 2011..with proinflammatory cytokines, the deubiquitinase A20 inducibly interacts with the regulatory molecules TAX1BP1, Itch and RNF11 to form the A20 ubiquitin-editing complex...
- Ubiquitin E3 ligase Itch negatively regulates osteoclast formation by promoting deubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6Hengwei Zhang
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 288:22359-68. 2013b>Itch is a ubiquitin E3 ligase that regulates protein stability. Itch(-/-) mice develop an autoimmune disease phenotype characterized by itchy skin and multiorgan inflammation...
- Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexesNoula Shembade
Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Science 327:1135-9. 2010..These findings suggest mechanism of A20 action in the inhibition of inflammatory signaling pathways...
- Phosphatidylinositol 4-kinase IIα function at endosomes is regulated by the ubiquitin ligase ItchJulia Mössinger
Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Takustraße 6, 14195 Berlin, Germany
EMBO Rep 13:1087-94. 2012..Here we identify the E3 ubiquitin ligase Itch as binding partner and regulator of PI4KIIα function...
- A discrete ubiquitin-mediated network regulates the strength of NOD2 signalingJustine T Tigno-Aranjuez
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Mol Cell Biol 33:146-58. 2013..and subsequent NOD2 signaling, this positive regulation is countered by another E3 ubiquitin ligase, ITCH, through direct ubiquitination of cIAP1. This ITCH-mediated ubiquitination leads to cIAP1's lysosomal degradation...
- The E3 ubiquitin ligase ITCH negatively regulates canonical Wnt signaling by targeting dishevelled proteinWei Wei
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Mol Cell Biol 32:3903-12. 2012..Here, we identify the HECT-containing Nedd4-like ubiquitin E3 ligase ITCH as a new Dvl-binding protein...
- PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4Fuping You
The Education Ministry Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China
Nat Immunol 10:1300-8. 2009..PCBP2 recruited the HECT domain-containing E3 ligase AIP4 to polyubiquitinate and degrade MAVS...
- MEKK1 binds HECT E3 ligase Itch by its amino-terminal RING motif to regulate Th2 cytokine gene expressionThomas Enzler
Stanford University School of Medicine, Stanford, CA 94305, USA
J Immunol 183:3831-8. 2009MEKK1-dependent signaling regulates HECT E3 ligase Itch, resulting in elevated catalytic activity. After TCR costimulation, MEKK1 predominantly induces JNK1 activation, whereas the related kinase MEKK2 regulates ERK5 activation...
- Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itchJoshua A Jadwin
Laboratory of Molecular Microbiology, NIAID, NIH, 4 Center Dr, Bethesda, MD 20892, USA
J Virol 84:704-15. 2010..However, low-level expression of the ubiquitin ligase Itch potently rescued the release and infectivity of MoMLV lacking PPPY function...
- C/EBPalpha and beta couple interfollicular keratinocyte proliferation arrest to commitment and terminal differentiationRodolphe G Lopez
EMBL Mouse Biology Unit, Monterotondo, 00016 Italy
Nat Cell Biol 11:1181-90. 2009..C/EBPs, therefore, couple basal keratinocyte cell cycle exit to commitment to differentiation through E2F repression and DNA binding, respectively, and may act to restrict the epidermal stem cell compartment...
- MKK4/SEK1 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase itchYoung Ho Ahn
Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
J Biol Chem 284:29399-404. 2009..MKK4 ubiquitination required JNK kinase activity. The JNK substrate Itch (a HECT domain-containing Nedd4-like ubiquitin protein ligase) bound to MKK4, ubiquitinated lysines 140 and 143, ..
- CTLA-4 (CD152) inhibits T cell function by activating the ubiquitin ligase ItchHolger Hoff
Deutsches Rheuma ForschungsZentrum Berlin, 10117 Berlin, Germany
Mol Immunol 47:1875-81. 2010..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...
- A model of partnership co-opted by the homeodomain protein TGIF and the Itch/AIP4 ubiquitin ligase for effective execution of TNF-alpha cytotoxicityChristine Demange
INSERM U, Paris, France
Mol Cell 36:1073-85. 2009..role of TGIF does not appear to rely on transcriptional modulation but instead is executed in conjunction with Itch/AIP4, an E3 ubiquitin ligase operating in TNF-alpha-induced apoptosis through its ability to target the caspase ..
- K33-linked polyubiquitination of T cell receptor-zeta regulates proteolysis-independent T cell signalingHaining Huang
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Immunity 33:60-70. 2010..E3 ubiquitin ligases such as Cbl-b and Itch have been implicated in T cell activation and tolerance induction...
- Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonistsElena Scotti
Howard Hughes Medical Institute, UCLA School of Medicine, Box 951662, Los Angeles, CA 90095 1662, USA
Mol Cell Biol 31:1885-93. 2011..These results demonstrate that the LXR-Idol pathway is an important contributor to feedback inhibition of the LDLR by sterols and a biological determinant of cellular LDL uptake...
- The E3 ligase Itch is a negative regulator of the homeostasis and function of hematopoietic stem cellsChozhavendan Rathinam
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
Nat Immunol 12:399-407. 2011..Here we showed that the E3 ubiquitin ligase Itch negatively regulated the development and function of HSCs...
- The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammationNeesar Ahmed
Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA
Nat Immunol 12:1176-83. 2011..Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs...
- ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathwaysMingfang Tao
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Curr Biol 19:1255-63. 2009....
- A C-terminal sequence in the guanine nucleotide exchange factor Sec7 mediates Golgi association and interaction with the Rsp5 ubiquitin ligaseDeborah A Klos Dehring
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA
J Biol Chem 283:34188-96. 2008..These observations identify a new functional region within the Sec7/BIG family of Arf GEFs that is required for trans-Golgi network localization...
- Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitinationTung Liang Lee
Graduate Institute of Life Sciences, National Defense Medical Center, Neihu, Taipei 114, Taiwan, ROC
Biochem Biophys Res Commun 375:326-30. 2008..We describe the first in vivo evidence for the interaction between p45/NF-E2 and the E3 ubiquitin ligase Itch, and the subsequent ubiquitination of p45/NF-E2 by Itch...
- The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulumS Fang
Regulation of Protein Function Laboratory, Center for Cancer Research, National Cancer Institute, Building 10, Room 1B34, 9000 Rockville Pike, Bethesda, MD 20892 1152, USA
Proc Natl Acad Sci U S A 98:14422-7. 2001..gp78 has thus been found to be an example of a mammalian cellular E3 intrinsic to the ER, suggesting a potential link between ubiquitylation, ERAD, and metastasis...
- N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated proteinKieran F Harvey
Hanson Center for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia
J Biol Chem 277:9307-17. 2002..Based on previous observations in yeast, we propose that N4WBP5 may act as an adaptor for Nedd4-like proteins and their putative targets to control ubiquitin-dependent protein sorting and trafficking...
- The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itchAndreas Traweger
Institute of Molecular Biology, Austrian Academy of Sciences, 5020 Salzburg, Austria
J Biol Chem 277:10201-8. 2002..two-hybrid screening we have identified a novel interaction between occludin and the E3 ubiquitin-protein ligase Itch, a member of the HECT domain-containing ubiquitin-protein ligases...
- Regulation of immune responses by E3 ubiquitin-protein ligasesNan Fang
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, Calif, USA
Curr Dir Autoimmun 5:161-75. 2002
- Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signalingAkiko Ikeda
Department of Microbiology Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA
J Virol 77:5529-34. 2003..of Nedd4 family E3s in LMP2A B-cell signaling, LMP2A transgenic (LMP2A(+)) mice were crossed with mice with the Itch-deficient (Itch(-/-)) background...
- Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylationYongli Bai
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
Mol Cell 15:825-31. 2004..Here we show that loss of Itch E3 ligase in mouse embryonic fibroblasts (MEFs) results in reduced susceptibility of TGF-beta-induced cell growth ..
- Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expressionTiffany A Mathews
Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, PA 16802 6300, USA
J Neurosci Methods 140:169-81. 2004..Furthermore, use of zero net flux microdialysis appears warranted in investigations of serotonergic synaptic function where modest changes in extracellular 5-HT are thought to occur in response to altered uptake...
- Phosphorylation of either Ser16 or Thr30 does not disrupt the structure of the Itch E3 ubiquitin ligase third WW domainAlison Z Shaw
ICREA and the Biomedical Research Institute of Barcelona, Barcelona Science Park, Barcelona, Spain
Proteins 60:558-60. 2005
- The tyrosine kinase c-Abl protects c-Jun from ubiquitination-mediated degradation in T cellsBeixue Gao
Department of Otolaryngology Head and Neck Surgery, University of Missouri Columbia School of Medicine, Columbia, Missouri 65212, USA
J Biol Chem 281:29711-8. 2006..We have previously demonstrated that c-Jun is a substrate of Itch, a HECT-type E3 ubiquitin ligase. c-Jun is also a substrate of the tyrosine kinase c-Abl...
- Itch genetically interacts with Notch1 in a mouse autoimmune disease modelLydia E Matesic
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Hum Mol Genet 15:3485-97. 2006..Phylogenetic and in vitro analyses suggest that Itch is a negative regulator of Notch signaling...
- Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammationPaula M Oliver
Howard Hughes Medical Institute, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colorado 80206, USA
Immunity 25:929-40. 2006..This phenotype resembled that of Itchy mutant mice, suggesting that Ndfip1 might affect the function of Itch, an E3 ubiquitin ligase...
- Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junctionZhonghua Lu
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
J Cell Biol 177:1077-89. 2007..These results identify a synapse-associated E3 ubiquitin ligase as an important regulator of MuSK signaling...
- Itch inhibition regulates chemosensitivity in vitroT M Hansen
Medical Research Council, Toxicology Unit, Hodgkin Building, P O Box 138, Leicester University, Lancaster Road, Leicester LE1 9HN, UK
Biochem Biophys Res Commun 361:33-6. 2007b>Itch is a member of the HECT family of ubiquitin E3 ligases, and regulates the stability of several proteins involved in response to genotoxic stress...
- Ubiquitinylation of Ig beta dictates the endocytic fate of the B cell antigen receptorMiao Zhang
Section of Rheumatology, Department of Medicine, University of Chicago, IL 60637, USA
J Immunol 179:4435-43. 2007..demonstrate that the Ig beta component of the BCR is diubiquitinylated and that this is dependent on the E3 ligase Itch. Itch-/- B lymphocytes manifest both a defect in ligand-induced BCR internalization and endocytic trafficking to ..
- The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20Noula Shembade
Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
Nat Immunol 9:254-62. 2008..Here we demonstrate that the regulatory molecule TAX1BP1 recruited the E3 ligase Itch to A20 via two 'PPXY' motifs...
- Itch-/- alphabeta and gammadelta T cells independently contribute to autoimmunity in Itchy miceValentino Parravicini
Division of Molecular Immunology, Medical Research Council, National Institute for Medical Research, London, UK
Blood 111:4273-7282. 2008..Itchy mice lack the E3 ligase, Itch, and show dysregulation of T lymphocytes and the induction of a lethal autoimmune inflammatory condition...
- AIP4/Itch regulates Notch receptor degradation in the absence of ligandPatricia Chastagner
Unite de Signalisation Moleculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur, Paris, France
PLoS ONE 3:e2735. 2008..The mammalian ortholog of Su(dx), Itch/AIP4, has been shown to have multiple substrates, including Notch, but the precise events regulated by Itch/AIP4 in ..
- Molecular genetic characterization of six recessive viable alleles of the mouse agouti locusC M Hustad
Mammalian Genetics Laboratory, NCI Frederick Cancer Research and Development Center, Maryland 21702, USA
Genetics 140:255-65. 1995..Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder...