ITCH

Summary

Gene Symbol: ITCH
Description: itchy E3 ubiquitin protein ligase
Alias: ADMFD, AIF4, AIP4, NAPP1, E3 ubiquitin-protein ligase Itchy homolog, HECT-type E3 ubiquitin transferase Itchy homolog, NFE2-associated polypeptide 1, atrophin-1 interacting protein 4, itchy E3 ubiquitin protein ligase homolog
Species: human
Products:     ITCH

Top Publications

  1. Ho K, Zhou Z, She Y, Chun A, Cyr T, Yang X. Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability [corrected]. Proc Natl Acad Sci U S A. 2011;108:4870-5 pubmed publisher
    ..In this study, we have identified Itch, a HECT class E3 ubiquitin ligase, as a unique binding partner of LATS1...
  2. Winberg G, Matskova L, Chen F, Plant P, Rotin D, Gish G, et al. Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases. Mol Cell Biol. 2000;20:8526-35 pubmed
    ..the PPPPY motifs of LMP2A bind multiple WW domains of E3 protein-ubiquitin ligases of the Nedd4 family, including AIP4 and KIAA0439, and demonstrate that AIP4 and KIAA0439 form physiological complexes with LMP2A in EBV-positive B ..
  3. Sundvall M, Korhonen A, Paatero I, Gaudio E, Melino G, Croce C, et al. Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms. Proc Natl Acad Sci U S A. 2008;105:4162-7 pubmed publisher
    ..and endocytosis of CYT-1 isoforms and provided a binding site for a WW domain-containing ubiquitin ligase Itch. Itch catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into intracellular vesicles, and ..
  4. Slagsvold T, Marchese A, Brech A, Stenmark H. CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4. EMBO J. 2006;25:3738-49 pubmed
    ..CISK strongly interacts and colocalizes with the E3 ubiquitin ligase AIP4, which is important for the ubiquitin-dependent lysosomal degradation of CXCR4...
  5. Lohr N, Molleston J, Strauss K, Torres Martinez W, Sherman E, Squires R, et al. Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease. Am J Hum Genet. 2010;86:447-53 pubmed publisher
    Ubiquitin ligases play an important role in the regulation of the immune system. Absence of Itch E3 ubiquitin ligase in mice has been shown to cause severe autoimmune disease...
  6. Perry W, Hustad C, Swing D, O Sullivan T, Jenkins N, Copeland N. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nat Genet. 1998;18:143-6 pubmed
    ..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...
  7. Wei W, Li M, Wang J, Nie F, Li L. The E3 ubiquitin ligase ITCH negatively regulates canonical Wnt signaling by targeting dishevelled protein. Mol Cell Biol. 2012;32:3903-12 pubmed publisher
    ..Here, we identify the HECT-containing Nedd4-like ubiquitin E3 ligase ITCH as a new Dvl-binding protein...
  8. Milewska M, McRedmond J, Byrne P. Identification of novel spartin-interactors shows spartin is a multifunctional protein. J Neurochem. 2009;111:1022-30 pubmed publisher
    ..published information about spartin interaction with ubiquitin and the E3 ubiquitin-protein ligases, AIP4/Itch and AIP5/WWP1...
  9. Fang D, Kerppola T. Ubiquitin-mediated fluorescence complementation reveals that Jun ubiquitinated by Itch/AIP4 is localized to lysosomes. Proc Natl Acad Sci U S A. 2004;101:14782-7 pubmed
    ..Mutation of a recognition sequence for the E3 ligase Itch/AIP4 prevented Jun ubiquitination and stabilized it in cells...

More Information

Publications63

  1. Woelk T, Oldrini B, Maspero E, Confalonieri S, Cavallaro E, Di Fiore P, et al. Molecular mechanisms of coupled monoubiquitination. Nat Cell Biol. 2006;8:1246-54 pubmed
    ..Thus, our results clarify the mechanism of coupled monoubiquitination and identify the ubiquitination of E3 ligases as a critical determinant in this process. ..
  2. Courbard J, Fiore F, Adélaïde J, Borg J, Birnbaum D, Ollendorff V. Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH. J Biol Chem. 2002;277:45267-75 pubmed
    ..elegans library using the two-hybrid procedure in yeast, we found a novel interaction between Hsa-CBLC and Hsa-AIP4 or its C. elegans counterpart Cel-WWP1. Hsa-AIP4 and Cel-WWP1 are also ubiquitin E3 ligases...
  3. Oberst A, Malatesta M, Aqeilan R, Rossi M, Salomoni P, Murillas R, et al. The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proc Natl Acad Sci U S A. 2007;104:11280-5 pubmed
    ..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...
  4. Venuprasad K, Huang H, Harada Y, Elly C, Subramaniam M, Spelsberg T, et al. The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1. Nat Immunol. 2008;9:245-53 pubmed publisher
    ..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...
  5. Lallemand F, Seo S, Ferrand N, Pessah M, L Hoste S, Rawadi G, et al. AIP4 restricts transforming growth factor-beta signaling through a ubiquitination-independent mechanism. J Biol Chem. 2005;280:27645-53 pubmed
    ..Using the two-hybrid screen, we identified atrophin 1-interacting protein 4 (AIP4) as an E3 ubiquitin ligase that specifically targets Smad7 for ubiquitin-dependent degradation without affecting ..
  6. Rauch S, Martin Serrano J. Multiple interactions between the ESCRT machinery and arrestin-related proteins: implications for PPXY-dependent budding. J Virol. 2011;85:3546-56 pubmed publisher
    ..virus type 1 (HTLV-1) access the ESCRT pathway via interaction with HECT ubiquitin ligases (WWP1, WWP2, and Itch). However, the mechanism of ESCRT-III recruitment in this context remains elusive...
  7. Shembade N, Parvatiyar K, Harhaj N, Harhaj E. The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling. EMBO J. 2009;28:513-22 pubmed publisher
    ..Our studies reveal that RNF11, together with TAX1BP1 and Itch, is an essential component of an A20 ubiquitin-editing protein complex that ensures transient activation of ..
  8. Azakir B, Desrochers G, Angers A. The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid. FEBS J. 2010;277:1319-30 pubmed publisher
    ..Here, we provide evidence that tBid is a substrate of the ubiquitin ligase Itch, which can specifically interact with and ubiquitinate tBid, but not intact Bid...
  9. Sheng Y, Hong J, Doherty R, Srikumar T, Shloush J, Avvakumov G, et al. A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen. Mol Cell Proteomics. 2012;11:329-41 pubmed publisher
    ..Our data set represents the first comprehensive analysis of E2-HECT E3 interactions, and thus provides a framework for better understanding the molecular mechanisms of ubiquitylation. ..
  10. Ishihara T, Tsuda H, Hotta A, Kozaki K, Yoshida A, Noh J, et al. ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridization. Cancer Sci. 2008;99:1940-9 pubmed publisher
    ..aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11...
  11. Marchese A, Raiborg C, Santini F, Keen J, Stenmark H, Benovic J. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev Cell. 2003;5:709-22 pubmed
    ..Here we report that the Nedd4-like E3 ubiquitin ligase AIP4 mediates ubiquitination of CXCR4 at the plasma membrane, and of the ubiquitin binding protein Hrs on endosomes...
  12. Santonico E, Belleudi F, Panni S, Torrisi M, Cesareni G, Castagnoli L. Multiple modification and protein interaction signals drive the Ring finger protein 11 (RNF11) E3 ligase to the endosomal compartment. Oncogene. 2010;29:5604-18 pubmed publisher
    ..moieties and that loss of acylation severely impairs the in vivo ubiquitination mediated by the HECT E3-ligases Itch and Nedd4...
  13. Bhandari D, Robia S, Marchese A. The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. Mol Biol Cell. 2009;20:1324-39 pubmed publisher
    The E3 ubiquitin ligase atrophin interacting protein 4 (AIP4) mediates ubiquitination and down-regulation of the chemokine receptor CXCR4...
  14. Salah Z, Melino G, Aqeilan R. Negative regulation of the Hippo pathway by E3 ubiquitin ligase ITCH is sufficient to promote tumorigenicity. Cancer Res. 2011;71:2010-20 pubmed publisher
    ..In this study, we report that the E3 ubiquitin ligase ITCH regulates stability of LATS1, a serine/threonine kinase in the Hippo pathway, through protein-protein interaction ..
  15. Gao B, Lee S, Fang D. The tyrosine kinase c-Abl protects c-Jun from ubiquitination-mediated degradation in T cells. J Biol Chem. 2006;281:29711-8 pubmed
    ..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...
  16. Rossi M, De Laurenzi V, Munarriz E, Green D, Liu Y, Vousden K, et al. The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J. 2005;24:836-48 pubmed
    ..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...
  17. Scialpi F, Malatesta M, Peschiaroli A, Rossi M, Melino G, Bernassola F. Itch self-polyubiquitylation occurs through lysine-63 linkages. Biochem Pharmacol. 2008;76:1515-21 pubmed publisher
    b>Itch, an E3 protein ubiquitin ligase (E3), which belongs to the homologous to E6-AP carboxy terminus (HECT)-type subfamily, catalyzes its own ubiquitylation...
  18. Wood J, Yuan J, Margolis R, Colomer V, Duan K, Kushi J, et al. Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins. Mol Cell Neurosci. 1998;11:149-60 pubmed
    ..AIP2/WWP2, AIP4, and AIP5/WWP1 are highly homologous, each having four WW domains and a HECT domain characteristic of ubiquitin ..
  19. McGill M, McGlade C. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J Biol Chem. 2003;278:23196-203 pubmed
    ..In agreement we demonstrate that Numb interacts with the cytosolic HECT domain-containing E3 ligase Itch and that Numb and Itch act cooperatively to promote ubiquitination of membrane-tethered Notch1...
  20. Kitching R, Wong M, Koehler D, Burger A, Landberg G, Gish G, et al. The RING-H2 protein RNF11 is differentially expressed in breast tumours and interacts with HECT-type E3 ligases. Biochim Biophys Acta. 2003;1639:104-12 pubmed
    ..Our GST-pulldown and immunoprecipitation results indicate that RNF11 interacts with the E3 ligase AIP4 when coexpressed with RNF11 in mammalian cells.
  21. Angers A, Ramjaun A, McPherson P. The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system. J Biol Chem. 2004;279:11471-9 pubmed
    ..We have identified the E3 ubiquitin ligase itch/AIP4 as an endophilin A1-binding partner...
  22. Rossi M, Aqeilan R, Neale M, Candi E, Salomoni P, Knight R, et al. The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc Natl Acad Sci U S A. 2006;103:12753-8 pubmed
    ..that the Hect (homologous to the E6-associated protein C terminus)-containing Nedd4-like ubiquitin protein ligase Itch binds, ubiquitylates, and promotes the degradation of p63...
  23. Bhandari D, Trejo J, Benovic J, Marchese A. Arrestin-2 interacts with the ubiquitin-protein isopeptide ligase atrophin-interacting protein 4 and mediates endosomal sorting of the chemokine receptor CXCR4. J Biol Chem. 2007;282:36971-9 pubmed
    ..CXCR4 is rapidly targeted for lysosomal degradation by the E3 ubiquitin ligase atrophin-interacting protein 4 (AIP4)...
  24. Wang C, An J, Zhang P, Xu C, Gao K, Wu D, et al. The Nedd4-like ubiquitin E3 ligases target angiomotin/p130 to ubiquitin-dependent degradation. Biochem J. 2012;444:279-89 pubmed publisher
    ..neural-precursor-cell-expressed developmentally down-regulated)-like ubiquitin E3 ligases, Nedd4, Nedd4-2 and Itch, as the ubiquitin E3 ligases for the long isoform of AMOT, AMOT/p130...
  25. Zhang P, Wang C, Gao K, Wang D, Mao J, An J, et al. The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. J Biol Chem. 2010;285:8869-79 pubmed publisher
    ..Here, we report that TXNIP undergoes proteasomal degradation in cells. We identify Itch as the E3 ubiquitin ligase for TXNIP...
  26. Panner A, Crane C, Weng C, Feletti A, Parsa A, Pieper R. A novel PTEN-dependent link to ubiquitination controls FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res. 2009;69:7911-6 pubmed publisher
    ..Total levels of the candidate FLIP(S) E3 ubiquitin ligase atrophin-interacting protein 4 (AIP4) were comparable in PTEN wild-type (WT) and PTEN mutant GBM cells, although in PTEN-deficient cells, AIP4 was ..
  27. Edwards T, Clowes V, Tsang H, Connell J, Sanderson C, Luzio J, et al. Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5. Biochem J. 2009;423:31-9 pubmed publisher
    ..demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1)...
  28. Mund T, Pelham H. Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP proteins. EMBO Rep. 2009;10:501-7 pubmed publisher
    ..membrane proteins, NDFIP1 and NDFIP2 (NEDD4 family-interacting proteins), activate the catalytic activity of ITCH and of several other HECT ligases by binding to them...
  29. Eastman S, Yassaee M, Bieniasz P. A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover. J Cell Biol. 2009;184:881-94 pubmed publisher
    ..These experiments suggest functions for ubiquitin ligases and SPG20 in the regulation of LD turnover and potential pathological mechanisms in Troyer syndrome...
  30. Azakir B, Angers A. Reciprocal regulation of the ubiquitin ligase Itch and the epidermal growth factor receptor signaling. Cell Signal. 2009;21:1326-36 pubmed publisher
    ..we demonstrate that treatment of cells with EGF leads to JNK-dependent phosphorylation of the ubiquitin ligase Itch, stimulating Itch ligase activity...
  31. Harvey K, Shearwin Whyatt L, Fotia A, Parton R, Kumar S. N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. J Biol Chem. 2002;277:9307-17 pubmed
    ..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. ..
  32. Adler J, Heller B, Bringman L, Ranahan W, Cocklin R, Goebl M, et al. Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth. J Biol Chem. 2013;288:15181-93 pubmed publisher
    ..This study describes how Amot130 through binding and activating the ubiquitin ligase AIP4/Itch achieves these effects. AIP4 is found to bind and ubiquitinate Amot130 at residue Lys-481...
  33. Gallagher E, Gao M, Liu Y, Karin M. Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change. Proc Natl Acad Sci U S A. 2006;103:1717-22 pubmed
    The E3 ubiquitin (Ub) ligase Itch is a critical regulator of T helper 2 (Th2) cytokine production through its ability to induce Ub-dependent JunB degradation...
  34. Chastagner P, Israel A, Brou C. Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains. EMBO Rep. 2006;7:1147-53 pubmed
    Deltex (DTX) and AIP4 are the human orthologues of the Drosophila deltex and Suppressor of deltex, which have been genetically described as being antagonistically involved in the Notch signalling pathway...
  35. Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico M, et al. Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Nat Cell Biol. 2006;8:1415-23 pubmed
    ..We demonstrate that the Hedgehog transcription factor Gli1 is targeted by Numb for Itch-dependent ubiquitination, which suppresses Hedgehog signals, thus arresting growth and promoting cell ..
  36. Shembade N, Harhaj N, Parvatiyar K, Copeland N, Jenkins N, Matesic L, et al. The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol. 2008;9:254-62 pubmed publisher
    ..Here we demonstrate that the regulatory molecule TAX1BP1 recruited the E3 ligase Itch to A20 via two 'PPXY' motifs...
  37. Di Marcotullio L, Greco A, Mazza D, Canettieri G, Pietrosanti L, Infante P, et al. Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal. Oncogene. 2011;30:65-76 pubmed publisher
    ..of an ubiquitin-mediated mechanism of Gli1 degradation, promoted by the coordinated action of the E3 ligase Itch and the adaptor protein Numb...
  38. Rossi M, Inoue S, Walewska R, Knight R, Dyer M, Cohen G, et al. Caspase cleavage of Itch in chronic lymphocytic leukemia cells. Biochem Biophys Res Commun. 2009;379:659-64 pubmed publisher
    ..Here we show that upon induction of apoptosis the ubiquitin ligase Itch is processed by caspases both in vitro and ex vivo in cells from patients with chronic lymphocytic leukemia (CLL)...
  39. Xu J, Paquet M, Lau A, Wood J, Ross C, Hall R. beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 (MAGI-2). Differential regulation of receptor internalization by MAGI-2 and PSD-95. J Biol Chem. 2001;276:41310-7 pubmed
  40. Venuprasad K. Cbl-b and itch: key regulators of peripheral T-cell tolerance. Cancer Res. 2010;70:3009-12 pubmed publisher
    E3 ligases Cbl-b and Itch have emerged as dominant "tolerogenic" regulators of T cells because their deficiency results in severe autoimmune diseases...
  41. Shenoy S, Xiao K, Venkataramanan V, Snyder P, Freedman N, Weissman A. Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor. J Biol Chem. 2008;283:22166-76 pubmed publisher
    ..ubiquitination and lysosomal degradation, whereas siRNA targeting the closely related E3 ligases Nedd4-2 or AIP4 did not...
  42. Chandrasekaran P, Buckley M, Moore V, Wang L, Kehrl J, Venkatesan S. HIV-1 Nef impairs heterotrimeric G-protein signaling by targeting G?(i2) for degradation through ubiquitination. J Biol Chem. 2012;287:41481-98 pubmed publisher
    ..Here, we report that a dominant effect of Nef is to trigger AIP4 E3 ligase-mediated G?(i2) ubiquitination, which leads to G?(i2) endolysosomal sequestration and destruction...
  43. Levy D, Reuven N, Shaul Y. A regulatory circuit controlling Itch-mediated p73 degradation by Runx. J Biol Chem. 2008;283:27462-8 pubmed publisher
    ..The level of p73 is regulated by the E3 ligase Itch. Itch levels are sharply reduced in response to DNA damage with concomitant p73 accumulation and activation...
  44. Shearwin Whyatt L, Brown D, Wylie F, Stow J, Kumar S. N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking. J Cell Sci. 2004;117:3679-89 pubmed
    ..We propose that N4WBP5A acts as an adaptor to recruit Nedd4 family ubiquitin-protein ligases to the protein trafficking machinery. ..
  45. Yang C, Zhou W, Jeon M, Demydenko D, Harada Y, Zhou H, et al. Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated tyrosine phosphorylation. Mol Cell. 2006;21:135-41 pubmed
    ..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...
  46. Qiu L, Joazeiro C, Fang N, Wang H, Elly C, Altman Y, et al. Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase. J Biol Chem. 2000;275:35734-7 pubmed
    Genetic 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...
  47. Mouchantaf R, Azakir B, McPherson P, Millard S, Wood S, Angers A. The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X. J Biol Chem. 2006;281:38738-47 pubmed
    b>Itch is a ubiquitin ligase that has been implicated in the regulation of a number of cellular processes...
  48. Salah Z, Cohen S, Itzhaki E, Aqeilan R. NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for degradation. Cell Cycle. 2013;12:3817-23 pubmed publisher
    ..These findings might be applied in the development of new therapeutic approaches through the activation of LATS1. ..
  49. Wegierski T, Hill K, Schaefer M, Walz G. The HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels. EMBO J. 2006;25:5659-69 pubmed
    ..of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel...
  50. Malik R, Soh U, Trejo J, Marchese A. Novel roles for the E3 ubiquitin ligase atrophin-interacting protein 4 and signal transduction adaptor molecule 1 in G protein-coupled receptor signaling. J Biol Chem. 2012;287:9013-27 pubmed publisher
    ..Ubiquitin modification of CXCR4 by the E3 ubiquitin ligase AIP4 is required for lysosomal sorting and degradation, which is mediated by the endosomal sorting complex required for ..
  51. Bai Y, Yang C, Hu K, Elly C, Liu Y. Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylation. Mol Cell. 2004;15:825-31 pubmed
    ..Here we show that loss of Itch E3 ligase in mouse embryonic fibroblasts (MEFs) results in reduced susceptibility of TGF-beta-induced cell growth ..
  52. Levy D, Adamovich Y, Reuven N, Shaul Y. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ. 2007;14:743-51 pubmed
    ..The ubiquitin E3 ligase Itch, like Yap1, interacts with p73...
  53. Agarwal N, Kim C, Kunkalla K, Konno H, Tjendra Y, Kwon D, et al. Active IKKβ promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma. Blood. 2016;127:605-15 pubmed publisher
    ..Tumor necrosis factor-α (TNFα) mediated IKKβ activation-impaired GLI1 binding with the E3 ubiquitin ligase-ITCH, leading to decreased K48-linked ubiquitination/degradation of GLI1...
  54. Panner A, Crane C, Weng C, Feletti A, Fang S, Parsa A, et al. Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res. 2010;70:5046-53 pubmed publisher
    ..We previously reported that a novel phosphatase and tensin homologue (PTEN)-Akt-atrophin-interacting protein 4 (AIP4) pathway regulates FLIP(S) ubiquitination and stability, although the means by which PTEN and Akt were linked to ..