Edward W Harhaj

Summary

Affiliation: University of Miami
Country: USA

Publications

  1. pmc Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, The University of Miami, Miami, FL 33136, USA
    EMBO J 26:3910-22. 2007
  2. pmc Deubiquitinases in the regulation of NF-κB signaling
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    Cell Res 21:22-39. 2011
  3. ncbi Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami School of Medicine, Miami, FL 33136, USA
    Virology 333:145-58. 2005
  4. ncbi Mechanisms of persistent NF-kappaB activation by HTLV-I tax
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami School of Medicine, Miami, FL 33136, USA
    IUBMB Life 57:83-91. 2005
  5. pmc The kinase IKKα inhibits activation of the transcription factor NF-κB by phosphorylating the regulatory molecule TAX1BP1
    Noula 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
  6. pmc Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes
    Noula 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
  7. pmc The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, The University of Miami, Miami, FL 33136, USA
    EMBO J 28:513-22. 2009
  8. pmc RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling
    Soratree Charoenthongtrakul
    Department of Microbiology and Immunology, The University of Miami, Miller School of Medicine, Miami, Florida, United States of America
    PLoS ONE 8:e53717. 2013
  9. pmc ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling
    Linlin Gao
    Department of Microbiology and Immunology, Graduate Program in Cancer Biology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 286:36592-602. 2011
  10. doi The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20
    Noula 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

Research Grants

Collaborators

Detail Information

Publications25

  1. pmc Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, The University of Miami, Miami, FL 33136, USA
    EMBO J 26:3910-22. 2007
    ..Thus, TAX1BP1 is pivotal for the termination of NF-kappaB and JNK signaling by functioning as an essential regulator of A20...
  2. pmc Deubiquitinases in the regulation of NF-κB signaling
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    Cell Res 21:22-39. 2011
    ..Understanding the mechanisms of NF-κB downregulation by specific DUBs such as A20 and CYLD may provide therapeutic opportunities for the treatment of chronic inflammatory diseases and cancer...
  3. ncbi Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami School of Medicine, Miami, FL 33136, USA
    Virology 333:145-58. 2005
    ..Collectively, these results indicate that CD40 is a novel Tax-regulated gene, and the regulation of CD40 by Tax may play a role in cellular activation and HTLV-I-induced disease pathogenesis...
  4. ncbi Mechanisms of persistent NF-kappaB activation by HTLV-I tax
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami School of Medicine, Miami, FL 33136, USA
    IUBMB Life 57:83-91. 2005
    ..The adaptor function of Tax appears to be a common and important mechanism for the pathological activation of both NF-kappaB pathways...
  5. pmc The kinase IKKα inhibits activation of the transcription factor NF-κB by phosphorylating the regulatory molecule TAX1BP1
    Noula 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
    ..IKKα therefore serves a key role in the negative feedback of NF-κB canonical signaling by orchestrating assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation...
  6. pmc Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes
    Noula 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...
  7. pmc The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, The University of Miami, Miami, FL 33136, USA
    EMBO J 28:513-22. 2009
    ..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 inflammatory signalling pathways...
  8. pmc RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling
    Soratree Charoenthongtrakul
    Department of Microbiology and Immunology, The University of Miami, Miller School of Medicine, Miami, Florida, United States of America
    PLoS ONE 8:e53717. 2013
    ..Collectively, these results indicate that RNF11 functions together with TAX1BP1 to restrict antiviral signaling and IFN-β production...
  9. pmc ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling
    Linlin Gao
    Department of Microbiology and Immunology, Graduate Program in Cancer Biology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 286:36592-602. 2011
    ..Together, these results suggest that ABIN1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and A20 to restrict antiviral signaling...
  10. doi The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20
    Noula 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
    ..Thus, our studies show a previously unappreciated complexity of A20 substrate recognition and inactivation whereby TAX1BP1 and Itch function as essential subunits of an A20 ubiquitin-editing complex...
  11. ncbi Activation of NF-kappa B by the human T cell leukemia virus type I Tax oncoprotein is associated with ubiquitin-dependent relocalization of I kappa B kinase
    Nicole S Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 282:4185-92. 2007
    ..Together, these results demonstrate that Tax induces relocalization of the IKK complex in a ubiquitin-dependent manner, and dynamic changes in the subcellular localization of the IKK complex may be critical for Tax function...
  12. pmc The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    J Virol 81:13735-42. 2007
    ..Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax-mediated NF-kappaB activation...
  13. pmc TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases
    Kislay Parvatiyar
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 285:14999-5009. 2010
    ..Collectively, our results demonstrate TBK1-IKKi to be novel substrates for A20 and further identify a novel mechanism whereby A20 and TAX1BP1 restrict antiviral signaling by disrupting a TRAF3-TBK1-IKKi signaling complex...
  14. pmc Deregulated expression of CD40 ligand in HTLV-I infection: distinct mechanisms of downregulation in HTLV-I-transformed cell lines and ATL patients
    Nicole S Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    Virology 362:99-108. 2007
    ..However, the CD40L gene is not silenced by methylation in ATL patients, thus CD40L is downregulated by distinct mechanisms in HTLV-I-transformed cell lines and ATL patients...
  15. ncbi Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation
    Gongxian Liao
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 279:26243-50. 2004
    ..These results suggest that induction of noncanonical NF-kappaB signaling may involve the rescue of NIK from TRAF3-mediated negative regulation...
  16. pmc Regulation of NF-κB by deubiquitinases
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL, USA
    Immunol Rev 246:107-24. 2012
    ..Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer...
  17. pmc Regulation of inflammatory and antiviral signaling by A20
    Kislay Parvatiyar
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    Microbes Infect 13:209-15. 2011
    ..A20 is a key regulator of inflammatory, antiviral and apoptotic signaling pathways. Here, we review recent advances illustrating the role of A20 as an essential negative regulator of inflammatory and antiviral signaling...
  18. pmc An RNA interference screen identifies the Deubiquitinase STAMBPL1 as a critical regulator of human T-cell leukemia virus type 1 tax nuclear export and NF-κB activation
    Alfonso Lavorgna
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, Florida, USA
    J Virol 86:3357-69. 2012
    ..Together, these results reveal that the deubiquitinase STAMBPL1 is a key regulator of Tax trafficking and function...
  19. pmc Regulation of NF-κB signaling by the A20 deubiquitinase
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA
    Cell Mol Immunol 9:123-30. 2012
    ..Recent studies also indicate that A20 is an important tumor suppressor that is inactivated in B-cell lymphomas. Therefore, targeting A20 may form the basis of novel therapies for autoimmune disease and lymphomas...
  20. ncbi Role of the proteasome in the downregulation of transcription factors NFkappaB and C/EBP in macrophages from tumor hosts
    Giselle Perry
    Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33236, USA
    Oncol Rep 23:875-81. 2010
    ..Thus, proteasome degradation may contribute, at least in part, to NFkappaB and C/EBP impairment in macrophages from tumor-bearers...
  21. ncbi Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax
    Timothy Alefantis
    Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University Hershey, 500 University Drive, PA 17033, USA
    J Biol Chem 278:21814-22. 2003
    ..These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal...
  22. pmc Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1
    Soratree Charoenthongtrakul
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    J Virol 85:6955-62. 2011
    ..Taken together, our results reveal that Tax inhibits antiviral signaling, in part, by hijacking an interferon regulatory protein...
  23. pmc IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma
    Juan Carlos Ramos
    Division of Hematology Oncology, Department of Medicine, University of Miami Miller School of Medicine, FL 33136, USA
    Blood 109:3060-8. 2007
    ..These molecular features may help guide treatment. AZT and IFN-alpha is a suppressive rather than a curative regimen, and patients in clinical remission should remain on maintenance therapy indefinitely...
  24. ncbi Mediators of central nervous system damage during the progression of human T-cell leukemia type I-associated myelopathy/tropical spastic paraparesis
    Kate Barmak
    Laboratory for Molecular Retrovirology and Viral Neuropathogenesis, Department of Microbiology and Immunology, The Pennsylvania State University, College of Medicine, Hershey 17033, USA
    J Neurovirol 9:522-9. 2003
    ..This review focuses on potential mechanisms of central nervous system (CNS) damage associated with the genesis of HAM/TSP following HTLV-I infection, focusing on the role of the Tax-specific CTL compartment...
  25. pmc Role of post-translational modifications of HTLV-1 Tax in NF-κB activation
    Noula Shembade
    Noula Shembade, Edward W Harhaj, Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
    World J Biol Chem 1:13-20. 2010
    ..In this review, we summarize the present knowledge on mechanisms underlying Tax-mediated NF-κB activation, with an emphasis on post-translational modifications of Tax...

Research Grants10

  1. Mechanisms of HTLV-I Tax-mediated NF-kB activation
    Edward W Harhaj; Fiscal Year: 2010
    ....
  2. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2010
    ..This proposal will provide mechanistic insight into how TAX1BP1, Itch and A20 function together to inactivate key signaling molecules and restrict inflammatory signaling pathways. ..
  3. Mechanisms of HTLV-I Tax-mediated NF-kB activation
    Edward Harhaj; Fiscal Year: 2009
    ....
  4. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward Harhaj; Fiscal Year: 2009
    ..This proposal will provide mechanistic insight into how TAX1BP1, Itch and A20 function together to inactivate key signaling molecules and restrict inflammatory signaling pathways. ..
  5. HTLV Deregulation of CD40(L) in Cancer&Neurodegeneration
    Edward Harhaj; Fiscal Year: 2007
    ..Completion of the proposed studies may lead to therapeutic strategies of immune modulation, which could prevent leukemia and/or neuroinflammatory disease. ..