Sankar Ghosh

Summary

Affiliation: Yale University
Country: USA

Publications

  1. pmc Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy
    Swarnali Acharyya
    Human Cancer Genetics Program and Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA
    J Clin Invest 117:889-901. 2007
  2. pmc CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis
    Jae Hyuck Shim
    Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520, USA
    J Cell Biol 172:1045-56. 2006
  3. pmc The kinase PDK1 integrates T cell antigen receptor and CD28 coreceptor signaling to induce NF-kappaB and activate T cells
    Sung Gyoo Park
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 10:158-66. 2009
  4. pmc Local treatment with the selective IkappaB kinase beta inhibitor NEMO-binding domain peptide ameliorates synovial inflammation
    Sander W Tas
    Division of Clinical Immunology and Rheumatology F4 218, Academic Medical Center University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands
    Arthritis Res Ther 8:R86. 2006
  5. ncbi request reprint PACT and PKR: turning on NF-kappa B in the absence of virus
    F D'Acquisto
    Section of Immunobiology, Department of Molecular Biophysics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Sci STKE 2001:re1. 2001
  6. ncbi request reprint Missing pieces in the NF-kappaB puzzle
    Sankar Ghosh
    Section of Immunobiology, Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Cell 109:S81-96. 2002
  7. doi request reprint New regulators of NF-kappaB in inflammation
    Sankar Ghosh
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nat Rev Immunol 8:837-48. 2008
  8. ncbi request reprint NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses
    S Ghosh
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Annu Rev Immunol 16:225-60. 1998
  9. ncbi request reprint PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation
    Ki Young Lee
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 308:114-8. 2005
  10. pmc TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo
    Jae Hyuck Shim
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 19:2668-81. 2005

Research Grants

  1. NF-kappaB: Biology and Pathology
    Sankar Ghosh; Fiscal Year: 2004
  2. Subversion of innate immune responses by Brucella
    Sankar Ghosh; Fiscal Year: 2006
  3. Regulation of NF-kB and 1kB Proteins
    Sankar Ghosh; Fiscal Year: 2007

Collaborators

Detail Information

Publications81

  1. pmc Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy
    Swarnali Acharyya
    Human Cancer Genetics Program and Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA
    J Clin Invest 117:889-901. 2007
    ..Collectively, these results underscore the critical role of NF-kappaB in the progression of muscular dystrophy and suggest the IKK/NF-kappaB signaling pathway as a potential therapeutic target for DMD...
  2. pmc CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis
    Jae Hyuck Shim
    Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520, USA
    J Cell Biol 172:1045-56. 2006
    ..Therefore, CHMP5 regulates late endosome function downstream of MVB formation, and the loss of CHMP5 enhances signal transduction by inhibiting lysosomal degradation of activated receptors...
  3. pmc The kinase PDK1 integrates T cell antigen receptor and CD28 coreceptor signaling to induce NF-kappaB and activate T cells
    Sung Gyoo Park
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 10:158-66. 2009
    ..CD28 facilitated NF-kappaB activation by regulating recruitment and phosphorylation of PDK1, which are necessary for efficient binding of PDK1 to protein kinase C-theta and the adaptor CARMA1 and thus for NF-kappaB induction...
  4. pmc Local treatment with the selective IkappaB kinase beta inhibitor NEMO-binding domain peptide ameliorates synovial inflammation
    Sander W Tas
    Division of Clinical Immunology and Rheumatology F4 218, Academic Medical Center University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands
    Arthritis Res Ther 8:R86. 2006
    ..These results indicate that IKK-beta-targeted NF-kappaB blockade using the NBD peptide could offer a new approach for the local treatment of arthritis...
  5. ncbi request reprint PACT and PKR: turning on NF-kappa B in the absence of virus
    F D'Acquisto
    Section of Immunobiology, Department of Molecular Biophysics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Sci STKE 2001:re1. 2001
    ..First, is PACT an alternative to dsRNA as a direct activator of the PKR-NF-kappaB pathway? Second, how is PACT itself activated and targeted to PKR? And third, what are the biological functions of PKR in the absence of viral infection?..
  6. ncbi request reprint Missing pieces in the NF-kappaB puzzle
    Sankar Ghosh
    Section of Immunobiology, Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Cell 109:S81-96. 2002
    ..A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK...
  7. doi request reprint New regulators of NF-kappaB in inflammation
    Sankar Ghosh
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nat Rev Immunol 8:837-48. 2008
    ..As a result, several new NF-kappaB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-kappaB...
  8. ncbi request reprint NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses
    S Ghosh
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Annu Rev Immunol 16:225-60. 1998
    ..In this review, we discuss some of these recent findings and their implications for the study of NF-kappa B...
  9. ncbi request reprint PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation
    Ki Young Lee
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 308:114-8. 2005
    ..Hence, PDK1 plays a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells...
  10. pmc TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo
    Jae Hyuck Shim
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 19:2668-81. 2005
    ..Therefore, our studies suggests that TAK1 acts as an upstream activating kinase for IKKbeta and JNK, but not IKKalpha, revealing an unexpectedly specific role of TAK1 in inflammatory signaling pathways...
  11. pmc Constitutively active NF-kappaB triggers systemic TNFalpha-dependent inflammation and localized TNFalpha-independent inflammatory disease
    Jie Dong
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Genes Dev 24:1709-17. 2010
    ..However, certain inflammatory disease states, such as keratitis or KCS, a condition that is seen in Sjogren's syndrome, are dependent on NF-kappaB, but are independent of TNFR1 signaling...
  12. doi request reprint Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor
    Meixiao Long
    Department of Immunobiology and Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 31:921-31. 2009
    ..Hence, NF-kappaB signaling pathway is a key regulator of Foxp3 expression during natural Treg cell development...
  13. pmc IkappaBbeta acts to inhibit and activate gene expression during the inflammatory response
    Ping Rao
    Department of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 466:1115-9. 2010
    ..Blocking IkappaBbeta might be a promising new strategy for selectively inhibiting the chronic phase of TNF-alpha production during the inflammatory response...
  14. ncbi request reprint Activation of NF-kappaB promotes the transition of large, CD43+ pre-B cells to small, CD43- pre-B cells
    Eijiro Jimi
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Int Immunol 17:815-25. 2005
    ..These data therefore indicate that activation of NF-kappaB in CD43(+) pre-B cells, as a result of signaling by the pre-B-cell receptor, facilitates the continued development of large, CD43(+) pre-B cells into small CD43(-) pre-B cells...
  15. ncbi request reprint Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo
    Eijiro Jimi
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Med 10:617-24. 2004
    ..Therefore, selective inhibition of NF-kappa B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption...
  16. ncbi request reprint A toll-like receptor that prevents infection by uropathogenic bacteria
    Dekai Zhang
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 303:1522-6. 2004
    ..Mice lacking TLR11 are highly susceptible to infection of the kidneys by uropathogenic bacteria, indicating a potentially important role for TLR11 in preventing infection of internal organs of the urogenital system...
  17. pmc Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor necrosis factor alpha-induced NF-kappa B activity
    Ralf B Marienfeld
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University Medical School, New Haven, CT 06520, USA
    Mol Cell Biol 26:9209-19. 2006
    ..Hence, our data provide novel insights into the role of the amino terminus of NEMO for the architecture of the IKK complex and its activation...
  18. pmc Repression of gene expression by unphosphorylated NF-kappaB p65 through epigenetic mechanisms
    Jie Dong
    Department of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 22:1159-73. 2008
    ..Therefore, unphosphorylated nuclear NF-kappaB can affect expression of genes not normally regulated by NF-kappaB through epigenetic mechanisms...
  19. pmc Regulation of IkappaBbeta expression in testis
    Lucy M Budde
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Mol Biol Cell 13:4179-94. 2002
    ..These results therefore suggest that IkappaBbeta may be a novel target for transcription factors of the HMG-box SRY/Sox family and imply a potential role for NF-kappaB/IkappaBbeta in spermatogenesis...
  20. pmc Differential role of the transcription factor NF-kappaB in selection and survival of CD4+ and CD8+ thymocytes
    Eijiro Jimi
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 29:523-37. 2008
    ....
  21. ncbi request reprint The interferon-inducible p202a protein modulates NF-kappaB activity by inhibiting the binding to DNA of p50/p65 heterodimers and p65 homodimers while enhancing the binding of p50 homodimers
    Xian Yong Ma
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    J Biol Chem 278:23008-19. 2003
    ..Transfected ectopic p202a increases the apoptotic effect of tumor necrosis factor (at least in part) by inhibiting NF-kappaB and its antiapoptotic activity...
  22. pmc Structure-based analysis of Toxoplasma gondii profilin: a parasite-specific motif is required for recognition by Toll-like receptor 11
    Kaury Kucera
    Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA
    J Mol Biol 403:616-29. 2010
    ..The putative TgPRF actin-binding surface includes the β-hairpin and diverges widely from the actin-binding surfaces of vertebrate profilins...
  23. pmc The NF-kappaB family of transcription factors and its regulation
    Andrea Oeckinghaus
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cold Spring Harb Perspect Biol 1:a000034. 2009
    ..This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation...
  24. ncbi request reprint RelB forms transcriptionally inactive complexes with RelA/p65
    Ralf Marienfeld
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University Medical School, New Haven, Connecticut 06520, USA
    J Biol Chem 278:19852-60. 2003
    ..Taken together, our findings demonstrate that sequestration of RelA in transcriptionally inactive RelA.RelB complexes provides a molecular mechanism that may explain the repressive role of RelB on NF-kappaB-dependent gene expression...
  25. ncbi request reprint Inhibition of NF-kappaB activation reduces the tissue effects of transgenic IL-13
    Svetlana P Chapoval
    Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 179:7030-41. 2007
    ..PS1145 inhibits caspase activation and up-regulates inhibitor of apoptosis protein cellular-inhibitor of apoptosis protein 1 (c-IAP-1). Therefore, NF-kappaB is an attractive target for immunotherapy of IL-13-mediated diseases...
  26. ncbi request reprint Regulating inducible transcription through controlled localization
    Elizabeth C Ziegler
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Sci STKE 2005:re6. 2005
    ..We also discuss the possibility that this more complex model of cytoplasmic retention might be applicable to a broader range of transcription factors and their associated signaling pathways...
  27. pmc Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL
    Dola Sengupta
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 184:956-64. 2010
    ..Therefore, TcpB represents a unique pathogen-derived molecule that suppresses host innate-immune responses by specifically targeting an individual adapter molecule in the TLR signaling pathway for degradation...
  28. ncbi request reprint The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1
    Haihong Zhong
    Immunobiology Section and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Mol Cell 9:625-36. 2002
    ..Our results demonstrate that phosphorylation of p65 determines whether it associates with either CBP or HDAC-1, ensuring that only p65 entering the nucleus from cytoplasmic NF-kappa B:Ikappa B complexes can activate transcription...
  29. pmc TLR signalling augments macrophage bactericidal activity through mitochondrial ROS
    A Phillip West
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 472:476-80. 2011
    ..These results reveal a novel pathway linking innate immune signalling to mitochondria, implicate mROS as an important component of antibacterial responses and further establish mitochondria as hubs for innate immune signalling...
  30. ncbi request reprint Amelioration of acute inflammation by systemic administration of a cell-permeable peptide inhibitor of NF-kappaB activation
    Paola Di Meglio
    Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Arthritis Rheum 52:951-8. 2005
    ..We used an experimental model of inflammation in mice, carrageenan-induced paw edema, to study the antiinflammatory effects of the NEMO-binding domain (NBD) peptide, which blocks activation of the inducible transcription factor NF-kappaB...
  31. ncbi request reprint Signaling to NF-kappaB
    Matthew S Hayden
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 18:2195-224. 2004
    ..In this review, we provide an overview of established NF-kappaB signaling pathways with focus on the current state of research into the mechanisms that regulate IKK activation and NF-kappaB transcriptional activity...
  32. ncbi request reprint Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300
    H Zhong
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Mol Cell 1:661-71. 1998
    ..Therefore, PKA regulates the transcriptional activity of NF-kappa B by modulating its interaction with CBP/p300...
  33. ncbi request reprint I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B
    J E Thompson
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520
    Cell 80:573-82. 1995
    ..Therefore, the overall activation of NF-kappa B consists of two overlapping phases, a transient phase mediated through I kappa B-alpha and a persistent phase mediated through I kappa B-beta...
  34. ncbi request reprint NF-kappaB, an evolutionarily conserved mediator of immune and inflammatory responses
    Changchun Xiao
    Section of Immunobiology, Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Adv Exp Med Biol 560:41-5. 2005
  35. doi request reprint Mitochondria in innate immune responses
    A Phillip West
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Rev Immunol 11:389-402. 2011
    ..Here, we review the emerging knowledge about the roles of mitochondria in innate immunity...
  36. ncbi request reprint Regulation of inducible gene expression by the transcription factor NF-kappaB
    S Ghosh
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06526, USA
    Immunol Res 19:183-9. 1999
    ....
  37. ncbi request reprint IkappaB kinases: kinsmen with different crafts
    M J May
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 284:271-3. 1999
  38. pmc Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis
    Changchun Xiao
    Section of Immunobiology, Howard Hughes Medical Institute, New Haven, CT 06520, USA
    Genes Dev 17:2933-49. 2003
    ..Therefore, these results show that Ecsit functions as an essential component in two important signal transduction pathways and establishes a novel role for Ecsit as a cofactor for Smad proteins in the Bmp signaling pathway...
  39. ncbi request reprint Inhibition of nuclear factor kappa B (NF-B): an emerging theme in anti-inflammatory therapies
    Fulvio D'Acquisto
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Mol Interv 2:22-35. 2002
    ..In this review, we describe various classes of NF-kappa B inhibitors and discuss important unresolved issues regarding their use...
  40. ncbi request reprint Antigen-receptor signaling to nuclear factor kappa B
    Jan Schulze-Luehrmann
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 25:701-15. 2006
    ..In this review, we provide an overview of the current state of research into the mechanisms that regulate AgR-mediated NF-kappaB transcriptional activity, with particular focus on the events leading to activation of the IKK complex...
  41. ncbi request reprint Characterization of the Ikappa B-kinase NEMO binding domain
    Michael J May
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University Medical School, New Haven, Connecticut 06520, USA
    J Biol Chem 277:45992-6000. 2002
    ....
  42. doi request reprint Shared principles in NF-kappaB signaling
    Matthew S Hayden
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 132:344-62. 2008
    ..Here, we attempt to synthesize some of the basic principles that have emerged from studies of NF-kappaB, and we aim to generate a more unified view of NF-kappaB regulation...
  43. ncbi request reprint SnapShot: NF-kappaB signaling pathways
    Matthew S Hayden
    Departments of Immunobiology and Molecular Biophysics and Biochemistry, Yale University School of Medicine, Newhaven, CT 06519, USA
    Cell 127:1286-7. 2006
  44. ncbi request reprint Differential phosphorylation of the signal-responsive domain of I kappa B alpha and I kappa B beta by I kappa B kinases
    Chun Wu
    Section of Immunobiology and the Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 278:31980-7. 2003
    ....
  45. ncbi request reprint Structure of NF-kappa B p50 homodimer bound to a kappa B site
    G Ghosh
    Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06510
    Nature 373:303-10. 1995
    ..The carboxy-terminal domains form a dimerization interface between beta-sheets using residues that are strongly conserved in the Rel family...
  46. ncbi request reprint Negative regulation of toll-like receptor-mediated signaling by Tollip
    Guolong Zhang
    Section of Immunobiology, Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520, USA
    J Biol Chem 277:7059-65. 2002
    ..Negative regulation of TLR signaling by Tollip may therefore serve to limit the production of proinflammatory mediators during inflammation and infection...
  47. pmc ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway
    E Kopp
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute HHMI, Yale University School of Medicine, New Haven, Connecticut 06520 USA
    Genes Dev 13:2059-71. 1999
    ..These results indicate an important role for ECSIT in signaling to NF-kappaB and suggest that processing of MEKK-1 is required for its function in the Toll/IL-1 pathway...
  48. ncbi request reprint A subclass of Ras proteins that regulate the degradation of IkappaB
    C Fenwick
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 287:869-73. 2000
    ..In cells, kappaB-Ras proteins are associated only with NF-kappaB:IkappaBbeta complexes and therefore may provide an explanation for the slower rate of degradation of IkappaBbeta compared with IkappaBalpha...
  49. ncbi request reprint The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism
    H Zhong
    Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cell 89:413-24. 1997
    ..Therefore, this pathway represents a novel mechanism for the cAMP-independent activation of PKA and the regulation of NF-kappaB activity...
  50. pmc Role of unphosphorylated, newly synthesized I kappa B beta in persistent activation of NF-kappa B
    H SuYang
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA
    Mol Cell Biol 16:5444-9. 1996
    ..It appears therefore that during prolonged stimulation, I kappa B beta functions as a chaperone for NF-kappa B by protecting it from I kappa B alpha and allowing it to be transported to the nucleus...
  51. ncbi request reprint Recognition and signaling by toll-like receptors
    A Phillip West
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Annu Rev Cell Dev Biol 22:409-37. 2006
    ..Here we review the mechanisms by which TLRs recognize pathogens and induce distinct signaling cascades...
  52. ncbi request reprint NF-kappaB and the immune response
    M S Hayden
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Oncogene 25:6758-80. 2006
    ..This review, therefore, describes the role of the NF-kappaB pathway in the development and functioning of the immune system...
  53. ncbi request reprint NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development
    R E Voll
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 13:677-89. 2000
    ..Therefore, signals emanating from the pre-TCR are mediated at least in part by NF-kappa B, which provides a selective survival signal for developing thymocytes with productive beta chain rearrangements...
  54. ncbi request reprint Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation
    B Li
    Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520 8011, USA
    Science 288:2219-22. 2000
    ..Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression...
  55. ncbi request reprint Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex
    M J May
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 289:1550-4. 2000
    ..The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity...
  56. ncbi request reprint Molecular evidence that human ocular ciliary epithelium expresses components involved in phototransduction
    R Bertazolli-Filho
    Department of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, New Haven, Connecticut 06510, USA
    Biochem Biophys Res Commun 284:317-25. 2001
    ..These results provide the first molecular evidence that components of a non-visual phototransduction pathway are expressed in the human ocular NPE ciliary epithelium, which may be linked to circadian entrainment tasks...
  57. ncbi request reprint Molecular cloning of the bovine CD9 antigen from ocular ciliary epithelial cells
    J M Martin-Alonso
    Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510
    J Biochem 112:63-7. 1992
    ..Normal and transformed cell lines established from the ocular ciliary epithelium exhibited significant levels of CD9 transcripts. These results raise questions regarding possible roles of CD9 in the anterior segment of the eye...
  58. ncbi request reprint beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta
    C Wu
    Section of Immunobiology, Department of Molecular Biophysics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 274:29591-4. 1999
    ..Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta...
  59. ncbi request reprint Cloning and characterization of the gene encoding mouse IkappaBbeta
    L M Budde
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Gene 247:279-86. 2000
    ..This suggests a close evolutionary relationship between these two IkappaB isoforms. The significance of this evolutionary relationship is discussed...
  60. pmc A glycine-rich region in NF-kappaB p105 functions as a processing signal for the generation of the p50 subunit
    L Lin
    Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, New Haven, Connecticut 06520, USA
    Mol Cell Biol 16:2248-54. 1996
    ..We have also demonstrated that the GRR can direct a similar processing event when it is inserted into a protein unrelated to the NF-kappaB family and that it is therefore an independent signal for processing...
  61. ncbi request reprint Tumor necrosis factor-alpha induces nuclear factor-kappaB-dependent TRPC1 expression in endothelial cells
    Biman C Paria
    Department of Pharmacology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 278:37195-203. 2003
    ..The augmented Ca2+ entry secondary to TRPC1 expression may be an important mechanism of endothelial injury induced by TNF-alpha...
  62. ncbi request reprint Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-kappaB activities
    Dongsoo Kim
    Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
    Immunity 16:9-21. 2002
    ..Therefore, we propose that E2A and HEB negatively regulate pre-TCR and TCR signaling and their removal causes hyperactivation and apoptosis of thymocytes...
  63. pmc Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease
    Anamitra Ghosh
    Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA
    Proc Natl Acad Sci U S A 104:18754-9. 2007
    ..These findings were specific because mutated NBD peptide had no effect. We conclude that selective inhibition of NF-kappaB activation by NBD peptide may be of therapeutic benefit for PD patients...
  64. ncbi request reprint Selective inhibition of NF-kappaB in dendritic cells by the NEMO-binding domain peptide blocks maturation and prevents T cell proliferation and polarization
    Sander W Tas
    Division of Clinical Immunology and Rheumatology, AMC University of Amsterdam, Amsterdam, The Netherlands
    Eur J Immunol 35:1164-74. 2005
    ..Also, these data indicate that the NBD peptide could be used as an elegant tool in DC based immunotherapy for unwanted cellular immune responses...
  65. ncbi request reprint Keeping cartographers busy
    Matthew S Hayden
    Nat Cell Biol 6:87-9. 2004
  66. ncbi request reprint NFkappaB activates in vivo the synthesis of inducible Cox-2 in the brain
    Agnes Nadjar
    Institut F Magendie, Unité de Neurobiologie Intégrative, Bordeaux Cedex, France
    J Cereb Blood Flow Metab 25:1047-59. 2005
    ..These findings strongly support the hypothesis that IL-1beta-induced NFkappaB activation plays a major role in transmission of immune signals from the periphery to the brain...
  67. ncbi request reprint Cytosolic, nuclear and nucleolar localization signals determine subcellular distribution and activity of the NF-kappaB inducing kinase NIK
    Andreas Birbach
    Department of Vascular Biology and Thrombosis Research, University of Vienna Medical School and Competence Center Bio Molecular Therapeutics, Schwarzspanierstr 17, 1090 Vienna, Austria
    J Cell Sci 117:3615-24. 2004
    ..Thus, subcellular distribution of NIK to different compartments might be a means of regulating the function of this kinase...
  68. ncbi request reprint A novel ubiquitin-like domain in IkappaB kinase beta is required for functional activity of the kinase
    Michael J May
    Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 279:45528-39. 2004
    ..Our findings therefore establish the ULD as a critical functional domain specific for IKKbeta that might play a role in dissociating IKKbeta from p65...
  69. pmc NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis
    Debajit K Biswas
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:10137-42. 2004
    ....
  70. ncbi request reprint Antineuroinflammatory effect of NF-kappaB essential modifier-binding domain peptides in the adoptive transfer model of experimental allergic encephalomyelitis
    Subhajit Dasgupta
    Section of Neuroscience, Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE 68583, USA
    J Immunol 173:1344-54. 2004
    ..Taken together, our results support the conclusion that NBD peptides are antineuroinflammatory, and that NBD peptides may have therapeutic effect in neuroinflammatory disorders such as multiple sclerosis...
  71. ncbi request reprint X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex
    Shiva Malek
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093 0359, USA
    J Biol Chem 278:23094-100. 2003
    ..NF-kappaB.DNA ternary complex formation. These unique structural features of IkappaBbeta may contribute to its ability to mediate persistent NF-kappaB activation...
  72. ncbi request reprint TLR11 activation of dendritic cells by a protozoan profilin-like protein
    Felix Yarovinsky
    Immunobiology Section, Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Science 308:1626-9. 2005
    ..Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens...
  73. ncbi request reprint NF-kappaB is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNFalpha
    Hideya Igarashi
    Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Int Immunol 18:653-9. 2006
    ..We conclude that while NF-kappaB plays a survival-promoting role in lymphoid progenitors, this may only be significant in circumstances such as transplantation when levels of TNFalpha are high...
  74. ncbi request reprint Role of nuclear factor-kappaB in the immune system and bone
    Eijiro Jimi
    Division of Molecular Biochemistry, Department of Biosciences, Science of Health Improvement, Kyushu Dental College, Kitakyushu shi, Japan
    Immunol Rev 208:80-7. 2005
    ..Furthermore, we discuss the possibility that inhibition of NF-kappaB might provide novel therapeutic approach for inhibiting bone destruction in rheumatoid arthritis...
  75. ncbi request reprint 'PPAR'ting ways with inflammation
    Shannon T Bailey
    Nat Immunol 6:966-7. 2005
  76. ncbi request reprint Noncanonical NF-kappaB signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation
    Sander W Tas
    Division of Clinical Immunology and Rheumatology, Academic Medical Center AMC University of Amsterdam, Amsterdam, The Netherlands
    Blood 110:1540-9. 2007
    ..These findings reveal an important role of the noncanonical NF-kappaB pathway in the regulation of immunity...
  77. pmc Involvement of phosphatidylinositol 3-kinase-mediated up-regulation of I kappa B alpha in anti-inflammatory effect of gemfibrozil in microglia
    Malabendu Jana
    Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA
    J Immunol 179:4142-52. 2007
    ....
  78. ncbi request reprint Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of NEMO interferes with the structure of the IKK complex and tumor necrosis factor-alpha-induced NF-kappaB activity
    Lysann Palkowitsch
    Institute of Physiological Chemistry, Ulm University, Albert Einstein Allee 11, Ulm 89081, Germany
    J Biol Chem 283:76-86. 2008
    ..In summary, we provide evidence for a signal-induced phosphorylation-dependent alteration of the IKK complex emphasizing the dynamic nature of this multisubunit kinase complex...
  79. ncbi request reprint CD8+ T cell apoptosis induced by Escherichia coli heat-labile enterotoxin B subunit occurs via a novel pathway involving NF-kappaB-dependent caspase activation
    Robert J Salmond
    University of Bristol, Department of Pathology and Microbiology, School of Medical Sciences, Bristol, GB
    Eur J Immunol 32:1737-47. 2002
    ..The data therefore indicate that EtxB-mediated apoptosis occurs via a novel pathway involving NF-kappaB...
  80. ncbi request reprint Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex
    Heidi Mendoza
    MRC Protein Phosphorylation Unit, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 409:711-22. 2008
    ....
  81. pmc Lipopolysaccharide induces CXCL2/macrophage inflammatory protein-2 gene expression in enterocytes via NF-kappaB activation: independence from endogenous TNF-alpha and platelet-activating factor
    Isabelle G De Plaen
    Department of Pediatrics Neonatology, Children s Memorial Hospital, Northwestern University Medical School, Chicago, IL 60614, USA
    Immunology 118:153-63. 2006
    ..In conclusion, CXCL2 gene is expressed in enterocytes in response to both TNF and LPS. LPS-induced CXCL2 expression is dependent on NF-kappaB activation via the IKK pathway. The effect of LPS is independent of endogenous TNF and PAF...

Research Grants4

  1. NF-kappaB: Biology and Pathology
    Sankar Ghosh; Fiscal Year: 2004
    ..Students will greatly benefit from exposure to many different biological processes, diseases and scientific approaches. ..
  2. Subversion of innate immune responses by Brucella
    Sankar Ghosh; Fiscal Year: 2006
    ..We are therefore proposing to characterize the role of TIRB in Brucella infection and we believe that our studies will help in the future development of therapeutic strategies, including vaccination, against human infection by Brucella. ..
  3. Regulation of NF-kB and 1kB Proteins
    Sankar Ghosh; Fiscal Year: 2007
    ..Name Organization Role on Project Sankar Ghosh Yale Medical School Principal Investigator Michael J...