Jonathan D Ashwell

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint T cells in G1 provide a memory-like response to secondary stimulation
    Ivana Munitic
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:4010-8. 2005
  2. ncbi request reprint Activating p38 MAPK: new tricks for an old kinase
    Paul R Mittelstadt
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell Cycle 4:1189-92. 2005
  3. ncbi request reprint Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP
    Guozhi Zhu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Curr Biol 17:1438-43. 2007
  4. pmc TWEAKing death
    Jonathan D Ashwell
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 182:15-7. 2008
  5. ncbi request reprint The many paths to p38 mitogen-activated protein kinase activation in the immune system
    Jonathan D Ashwell
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 6:532-40. 2006
  6. ncbi request reprint The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway
    Jesus M Salvador
    Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 6:396-402. 2005
  7. pmc T cell receptor-mediated activation of p38{alpha} by mono-phosphorylation of the activation loop results in altered substrate specificity
    Paul R Mittelstadt
    Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 284:15469-74. 2009
  8. ncbi request reprint Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling
    Yongge Zhao
    Laboratory of Immune Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 282:7777-82. 2007
  9. pmc Lack of the T cell-specific alternative p38 activation pathway reduces autoimmunity and inflammation
    Ludmila Jirmanova
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Blood 118:3280-9. 2011
  10. pmc Genetic disruption of p38alpha Tyr323 phosphorylation prevents T-cell receptor-mediated p38alpha activation and impairs interferon-gamma production
    Ludmila Jirmanova
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 113:2229-37. 2009

Collaborators

Detail Information

Publications39

  1. ncbi request reprint T cells in G1 provide a memory-like response to secondary stimulation
    Ivana Munitic
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:4010-8. 2005
    ....
  2. ncbi request reprint Activating p38 MAPK: new tricks for an old kinase
    Paul R Mittelstadt
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell Cycle 4:1189-92. 2005
    ..Here we discuss the structural and functional implications of this alternative p38 activation pathway, which may provide a new target for tissue-specific pharmacologic inhibition...
  3. ncbi request reprint Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP
    Guozhi Zhu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Curr Biol 17:1438-43. 2007
    ..These results reveal a physiologic role for optineurin in dampening TNFalpha signaling, and this role might provide an explanation for its association with glaucoma...
  4. pmc TWEAKing death
    Jonathan D Ashwell
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 182:15-7. 2008
    ..These findings not only extend our appreciation of how cell death pathways are kept in check in tumors, they reinforce the possible utility of induced cIDE (cIAP deficiency) in the selective elimination of neoplastic cells...
  5. ncbi request reprint The many paths to p38 mitogen-activated protein kinase activation in the immune system
    Jonathan D Ashwell
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 6:532-40. 2006
    ..These alternative pathways might have particular relevance for cells that participate in immune and inflammatory responses...
  6. ncbi request reprint The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway
    Jesus M Salvador
    Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 6:396-402. 2005
    ..Thus, constitutive activation of T cell p38 through the alternative pathway is prevented by Gadd45alpha, the absence of which results in p38 activation, T cell hyperproliferation and autoimmunity...
  7. pmc T cell receptor-mediated activation of p38{alpha} by mono-phosphorylation of the activation loop results in altered substrate specificity
    Paul R Mittelstadt
    Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 284:15469-74. 2009
    ..These findings suggest that T cells have evolved a mechanism to utilize p38 in a specialized manner independent of and distinct from the classical p38 MAPK signaling cascade...
  8. ncbi request reprint Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling
    Yongge Zhao
    Laboratory of Immune Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 282:7777-82. 2007
    ..Moreover, in the absence of c-IAP1 TNFR2-mediated p38 and JNK activation was prolonged. Thus, the ubiquitin protein ligase activity of c-IAP1 is responsible for regulating the duration of TNF signaling in primary cells expressing TNFR2...
  9. pmc Lack of the T cell-specific alternative p38 activation pathway reduces autoimmunity and inflammation
    Ludmila Jirmanova
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Blood 118:3280-9. 2011
    ..Thus, T cell-specific alternative activation of p38 is an important pathway in T-cell proliferation, Th skewing, and inflammatory autoimmunity, and may be an attractive tissue-specific target for intervention in these processes...
  10. pmc Genetic disruption of p38alpha Tyr323 phosphorylation prevents T-cell receptor-mediated p38alpha activation and impairs interferon-gamma production
    Ludmila Jirmanova
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 113:2229-37. 2009
    ..Thus, the Tyr323-dependent pathway and not the classic mitogen-activated protein (MAP) kinase cascade is the physiologic means of p38alpha activation through the TCR and is necessary for normal Th1 function but not Th1 generation...
  11. pmc TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 24:1886-98. 2005
    ..Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes...
  12. pmc The CD8+ memory T-cell state of readiness is actively maintained and reversible
    Atef Allam
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 114:2121-30. 2009
    ..Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance...
  13. ncbi request reprint Gadd45alpha regulates p38-dependent dendritic cell cytokine production and Th1 differentiation
    Ludmila Jirmanova
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 178:4153-8. 2007
    ..Therefore, Gadd45alpha has tissue-specific and opposing functions on p38 activity, and Gadd45alpha-regulated p38 activation in DCs is a critical event in Th1 polarization in vivo...
  14. pmc CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection
    David G Kugler
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases 2 Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute and 3 The Johns Hopkins University National Institutes of Health Graduate Partnership Program National Institutes of Health, Bethesda, MD 20892
    J Exp Med 210:1919-27. 2013
    ..In the case of T. gondii infection, this self-regulatory pathway is critical for preventing collateral tissue damage and promoting host survival. ..
  15. pmc Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation
    Dietrich B Conze
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 28:3538-47. 2008
    ..Thus, K63-linked polyubiquitination of proximal signaling proteins is a common mechanism used by diverse innate immune receptors for recruiting IKK and activating NF-kappaB...
  16. ncbi request reprint Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation
    Marco L Schito
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 176:4818-25. 2006
    ..In contrast, the abnormal thymic phenotype of Wip1-deficient mice was reversed in the absence of p53. These data suggest that Wip1 down-regulates p53 activation in the thymus and is required for normal alphabeta T cell development...
  17. pmc CD70 is downregulated by interaction with CD27
    Mirela Kuka
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 191:2282-9. 2013
    ..Therefore, the ability of CD70 to trigger costimulation is self-regulated when it binds its complementary receptor. ..
  18. ncbi request reprint Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 8:398-406. 2006
    ..These results provide a mechanism for NEMO's critical role in IKK activation, and a key to understanding the link between cytokine-receptor proximal signalling and IKK and NF-kappaB activation...
  19. pmc NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:3023-8. 2008
    ..Therefore, the regulated ubiquitination of Bcl10 and its recognition by NEMO are a critical link between the CBM complex, IKK recruitment, and NF-kappaB activation...
  20. pmc Balance between NF-κB p100 and p52 regulates T cell costimulation dependence
    Maria Letizia Giardino Torchia
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 190:549-55. 2013
    ..Thus, p100 represses and p52 promotes costimulation, and the ratio regulates T cell dependence on costimulatory signals...
  21. pmc CD70 deficiency impairs effector CD8 T cell generation and viral clearance but is dispensable for the recall response to lymphocytic choriomeningitis virus
    Ivana Munitic
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 190:1169-79. 2013
    ..Therefore, CD70 appears to be an important factor in the initiation of a robust and effective primary response but dispensable for CD8 T cell memory responses...
  22. ncbi request reprint Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases
    Jesus M Salvador
    Gene Response Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 6:390-5. 2005
    ..Thus, phosphorylation of Tyr323 dependent on the tyrosine kinase Lck and mediated by Zap70 serves as an important mechanism for TCR activation of p38 in T cells...
  23. ncbi request reprint Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis
    Ivana Munitic
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 104:4165-72. 2004
    ..Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells...
  24. pmc Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo
    Dietrich B Conze
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3002, Bethesda, MD 20892, USA
    Mol Cell Biol 25:3348-56. 2005
    ..Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism...
  25. pmc Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness
    Paul R Mittelstadt
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
    J Clin Invest 122:2384-94. 2012
    ....
  26. pmc c-IAP1 and c-IAP2 redundancy differs between T and B cells
    Maria Letizia Giardino Torchia
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    PLoS ONE 8:e66161. 2013
    ..Therefore, although c-IAP1 and c-IAP2 both can repress constitutive NF-κB activation, the relative importance of each varies according to cell type. ..
  27. pmc Identification and characterization of polyclonal αβ-T cells with dendritic cell properties
    Mirela Kuka
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Commun 3:1223. 2012
    ....
  28. ncbi request reprint Disruption of glucocorticoid receptor exon 2 yields a ligand-responsive C-terminal fragment that regulates gene expression
    Paul R Mittelstadt
    Building 10, Room 1B 40, National Institutes of Health, Bethesda, Maryland 20892
    Mol Endocrinol 17:1534-42. 2003
    ....
  29. pmc Non-canonical NF-κB activation and abnormal B cell accumulation in mice expressing ubiquitin protein ligase-inactive c-IAP2
    Dietrich B Conze
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    PLoS Biol 8:e1000518. 2010
    ..Thus, the c-IAP2/MALT1 fusion protein activates NF-κB by two distinct mechanisms, and loss of c-IAP2 E3 activity in vivo is sufficient to induce abnormalities common to MALT lymphoma...
  30. pmc Optineurin Insufficiency Impairs IRF3 but Not NF-κB Activation in Immune Cells
    Ivana Munitic
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    J Immunol 191:6231-40. 2013
    ..Importantly, Optn(470T) mice produced less IFN-β upon LPS challenge. Therefore, endogenous optineurin is dispensable for NF-κB activation but necessary for optimal IRF3 activation in immune cells. ..
  31. ncbi request reprint HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter
    Yili Yang
    Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:19482-7. 2002
    ....
  32. pmc IAPs: what's in a name?
    Srinivasa M Srinivasula
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 30:123-35. 2008
    ..Here, we review the current understanding of the roles of IAPs in apoptotic and nonapoptotic processes and explore the notion that the latter represents the primary physiologic activities of IAPs...
  33. pmc A method for high purity sorting of rare cell subsets applied to TDC
    Mirela Kuka
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Electronic address
    J Immunol Methods 400:111-6. 2013
    ..Cells obtained with this method are viable and can be used for in vitro characterization. Moreover, this double-round sorting strategy can be universally applied to the isolation of other rare cell subsets...
  34. ncbi request reprint A20: more than one way to skin a cat
    Srinivasa M Srinivasula
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 44:511-2. 2011
    ..In this issue of Molecular Cell, Skaug et al. (2011) propose a polyubiquitin-dependent, noncatalytic mechanism by which the deubiquitinase A20 inhibits IκB kinase and NF-κB activation...
  35. ncbi request reprint TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2
    Xiaoming Li
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nature 416:345-7. 2002
    ..These findings identify a physiologic role for c-IAP1 and define a mechanism by which TNF-RII-regulated ubiquitin protein ligase activity can potentiate TNF-induced apoptosis...
  36. ncbi request reprint Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome
    Jesus M Salvador
    Gene Response Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Immunity 16:499-508. 2002
    ....
  37. ncbi request reprint Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor alpha
    Denis Franchimont
    Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 168:2212-8. 2002
    ..These observations provide a mechanism by which glucocorticoids may have a positive influence on T cell survival and function...
  38. ncbi request reprint Regulation of constitutive TCR internalization by the zeta-chain
    Ugo D'Oro
    Chiron, Siena, Italy
    J Immunol 169:6269-78. 2002
    ....
  39. ncbi request reprint Mutually antagonistic signals regulate selection of the T cell repertoire
    Geoffrey L Stephens
    Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912 2600, USA
    Int Immunol 15:623-32. 2003
    ..Together, these results support a role for endogenous GC in balancing TCR-mediated signals during thymic selection...