Research Topics
Genomes and Genes
| Alain IsraelSummaryAffiliation: Institut Pasteur Country: France Publications
| Collaborators
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Detail Information
Publications
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domainE Laplantine
Unite de Signalisation Moleculaire et Activation Cellulaire, Institut Pasteur, URA 2582 CNRS, Paris, France
EMBO J 28:2885-95. 2009..We also demonstrate that the recently described binding of NEMO to linear poly-ubiquitin chains is dependent on the NOA alone and does not require the presence of the ZF...
The IKK complex: an integrator of all signals that activate NF-kappaB?A Israel
Unité de Biologie Moléculaire de l Expression Génique, URA 1773 CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
Trends Cell Biol 10:129-33. 2000....
The IKK complex, a central regulator of NF-kappaB activationAlain Israel
Unite de Signalisation Moleculaire et Activation Cellulaire, URA 2582 CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
Cold Spring Harb Perspect Biol 2:a000158. 2010..I will review here the genetic, biochemical, and structural data accumulated during the last 10 yr regarding the function of the three IKK subunits...
NF-kappaB activation: Nondegradative ubiquitination implicates NEMOAlain Israel
Unite de Signalisation Moleculaire et Activation Cellulaire, URA 2582 CNRS Institut Pasteur, 75015 Paris, France
Trends Immunol 27:395-7. 2006....
The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migrationEmmanuelle M Six
Unité de Biologie Moléculaire de l Expression Génique, URA 2582 CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
J Biol Chem 279:55818-26. 2004..These results point to a new, probably cell-autonomous function of Delta1, which is independent of its activity as a Notch ligand...
Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptorNeetu Gupta-Rossi
Unité de Biologie Moléculaire de l Expression Génique, URA 2582, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
J Cell Biol 166:73-83. 2004..We propose a new model where monoubiquitination and endocytosis of Notch are a prerequisite for its PS-dependent cleavage, and discuss its relevance for other gamma-secretase substrates...
AIP4/Itch regulates Notch receptor degradation in the absence of ligandPatricia Chastagner
Unite de Signalisation Moleculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur, Paris, France
PLoS ONE 3:e2735. 2008..The mammalian ortholog of Su(dx), Itch/AIP4, has been shown to have multiple substrates, including Notch, but the precise events regulated by Itch/AIP4 in the Notch pathway have not been identified yet...
The trimerization domain of NEMO is composed of the interacting C-terminal CC2 and LZ coiled-coil subdomainsFabrice Agou
Unité de Régulation Enzymatique des Activités Cellulaires, CNRS URA 2185, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
J Biol Chem 279:27861-9. 2004..This model is discussed in relation to the mechanism of activation of the IKK complex by upstream activators...
DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin bindingOlivera Grubisha
Unité de Biochimie Structurale et Cellulaire, Institut Pasteur, CNRS, URA 2185, Paris, France
J Mol Biol 395:89-104. 2010..Collectively, these data provide structural insights into how several pathological mutations within and outside of the CC2-LZ's NOA ubiquitin binding site affect IkappaB kinase activation in the NF-kappaB signaling pathway...
The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activitySara Farrah Heuss
Unite de Signalisation Moleculaire et Activation Cellulaire, Unité de Recherche Associées 2582, Centre National de la Recherche Scientifique, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France
Proc Natl Acad Sci U S A 105:11212-7. 2008....
Generation and characterization of mutant cell lines defective in gamma-secretase processing of Notch and amyloid precursor proteinAnnie Olry
Unite de Signalisation Moleculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
J Biol Chem 280:28564-71. 2005..The first mutation abolishes nicastrin production, and the second mutation, a point mutation in the ectodomain, abolishes nicastrin maturation. In both cases, gamma-secretase activity on Notch and APP is impaired...
Combined deficiency in IkappaBalpha and IkappaBepsilon reveals a critical window of NF-kappaB activity in natural killer cell differentiationSandrine I Samson
Unité des Cytokines et Développement Lymphoide, Institut Pasteur, 25 rue du Dr Roux, 75742 Paris, France
Blood 103:4573-80. 2004..These results define a critical window in NK cell development in which NF-kappaB levels may be tightly controlled...
Plk1-dependent phosphorylation of optineurin provides a negative feedback mechanism for mitotic progressionDavid Kachaner
Unite de Signalisation Moleculaire et Activation Cellulaire, Institut Pasteur, CNRS URA 2582, 75724 Paris Cedex 15, France
Mol Cell 45:553-66. 2012..Overall, these results highlight an important role of Optn in the spatial and temporal coordination of Plk1 activity...
The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradationJulien Moretti
Institut Pasteur and CNRS Unité de Recherche Associée URA 2582, Signalisation Moléculaire et Activation Cellulaire, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France
J Biol Chem 287:29429-41. 2012..These results characterize a new level of conserved regulation of Notch signaling by the ubiquitin system...
The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activationJulien Moretti
Institut Pasteur, Unité de Signalisation Moléculaire et Activation Cellulaire and CNRS URA 2582, rue du Dr Roux, Paris, France
PLoS Biol 8:e1000545. 2010..These data improve our knowledge of Notch signaling but also open new avenues of research on the Zomes family and the translation initiation factors...
NRP/Optineurin Cooperates with TAX1BP1 to potentiate the activation of NF-kappaB by human T-lymphotropic virus type 1 tax proteinChloé Journo
Unité d Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 3015, Institut Pasteur, Paris, France
PLoS Pathog 5:e1000521. 2009..Our data strongly suggest for the first time that NRP is a critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-kappaB activation...
Negative feedback loop in T cell activation through IkappaB kinase-induced phosphorylation and degradation of Bcl10Camille Lobry
Unite de Signalisation Moleculaire et Activation Cellulaire, Unité de Recherche Associée 2582, Centre National de la Recherche Scientifique, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
Proc Natl Acad Sci U S A 104:908-13. 2007..Mutants of Bcl10 in the IKK phosphorylation site are resistant to degradation, accumulate in the nucleus, and lead to an increase in IL-2 production after T cell antigen receptor stimulation...
The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathwayNeetu Gupta-Rossi
Unite de Signalisation Moleculaire et Activation Cellulaire, CNRS URA 2582, CNRS URA 2582, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
J Biol Chem 286:18720-30. 2011..These results suggest that after ligand-induced activation of Notch, the membrane-tethered form can be directed to different endocytic pathways leading to distinct fates...
IkappaBalpha/IkappaBepsilon deficiency reveals that a critical NF-kappaB dosage is required for lymphocyte survivalBertrand Goudeau
Unité de Biologie Moléculaire de l Expression Génique, Unite de Recherche Associee, Centre National de la Recherche Scientifique 2582, Unité de Biologie Moléculaire du Gène, Paris Cedex 15, France
Proc Natl Acad Sci U S A 100:15800-5. 2003..Because reduction or rise of NF-kappaB activity leads to similar dysfunction, they also reveal that only a narrow window of NF-kappaB activity is tolerated by lymphocytes...
Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chainsPatricia Chastagner
Unite de Signalisation Moleculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
EMBO Rep 7:1147-53. 2006..Furthermore, AIP4-generated polyubiquitin chains are mainly conjugated through lysine 29 of ubiquitin in vivo, indicating a link between this type of chain and lysosomal degradation...
Forebrain-specific neuronal inhibition of nuclear factor-kappaB activity leads to loss of neuroprotectionValérie Fridmacher
Unité de Biologie Moléculaire de l Expression Génique, Centre National de la Recherche Scientifique 2582, Institut Pasteur, Paris Cedex 15, France
J Neurosci 23:9403-8. 2003..These data demonstrate for the first time that neuron-restricted ablation of NF-kappaB-driven gene expression increases neurodegeneration. This might lead to the path for new treatments of neurodegenerative diseases...
Inhibition of NF-kappa B activation by peptides targeting NF-kappa B essential modulator (nemo) oligomerizationFabrice Agou
Unité de Régulation Enzymatique des Activités Cellulaires, CNRS URA 2185, 75724 Paris, France
J Biol Chem 279:54248-57. 2004..Our results provide the "proof of concept" for a new and promising strategy for the inhibition of NF-kappa B pathway activation through targeting the oligomerization state of the NEMO protein...
NEMO trimerizes through its coiled-coil C-terminal domainFabrice Agou
Unité de Régulation Enzymatique des Activités Cellulaires, Paris Cedex 15, France
J Biol Chem 277:17464-75. 2002..We propose a model in which the activation of the IKK complex occurs through the trimerization of NEMO upon binding to a not yet identified upstream activator...
The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translationAnne Puel
Laboratoire de Genetique Humaine des Maladies Infectieuses, Faculte de Medecine Necker-Enfants Malades, 75015 Paris, France
Am J Hum Genet 78:691-701. 2006..The residual production of an NH(2)-truncated NEMO protein was sufficient for normal fetal development and for the subsequent normal development of skin appendages but was insufficient for the development of protective immune responses...
A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiencyGilles Courtois
Unité de Biologie Moléculaire de l Expression Génique, Centre National de la Recherche Scientifique URA 2582, Institut Pasteur, Paris, France
J Clin Invest 112:1108-15. 2003..Our report highlights both the diversity of genotypes associated with EDA-ID and the diversity of immunologic phenotypes associated with mutations in different components of the NF-kappaB signaling pathway...
The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretaseEmmanuelle Six
Unité de Biologie Moléculaire de l Expression Génique, Unité de Recherche Associée 2582, Centre National de la Recherche Scientifique, Institut Pasteur, 75724 Paris Cedex 15, France
Proc Natl Acad Sci U S A 100:7638-43. 2003..Therefore Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus...
From calcium to NF-kappa B signaling pathways in neuronsAlain Lilienbaum
Unité de Biologie Moléculaire de l Expression Génique, URA 2582 CNRS, Institut Pasteur, 75724 Paris Cedex 15, France
Mol Cell Biol 23:2680-98. 2003..By using a global approach in studying signaling pathways in neurons, these results provide further evidence to validate the concept of networks of transducing cascades, specific to cells and to physiological situations...
Arachidonic acid differentially affects basal and lipopolysaccharide-induced sPLA(2)-IIA expression in alveolar macrophages through NF-kappaB and PPAR-gamma-dependent pathwaysMounia Alaoui-El-Azher
, Institut Pasteur, Paris, France
Mol Pharmacol 61:786-94. 2002..In contrast, the inhibition of LPS-stimulated sPLA(2)-IIA expression is mediated by cyclooxygenase-derived metabolites of AA and involves a PPAR-gamma-dependent pathway. These findings provide new insights for the treatment of ALI...
T-cell-receptor- and B-cell-receptor-mediated activation of NF-kappaB in lymphocytesRobert Weil
, , 2582 Centre National de la Recherche Scientifique, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France
Curr Opin Immunol 16:374-81. 2004....
Induction of the NF-kappaB cascade by recruitment of the scaffold molecule NEMO to the T cell receptorRobert Weil
Unité de Biologie Moléculaire de l Expression Génique, FRE 2364 Centre National de la Recherche Scientifique CNRS, 75724 Paris Cedex 15, France
Immunity 18:13-26. 2003..This study shows that the localization of NEMO to the immunological synapse is important for TCR-induced NF-kappaB activation and offers a powerful system to dissect the NF-kappaB cascade in T cells...
[Human pathologies associated with NF-kappaB defects]Gilles Courtois
, URA 2582 CNRS, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France
J Soc Biol 198:93-6. 2004..This gene encodes a protein which interacts with NEMO and exhibits deubiquitinase activity, therefore strengthening the recent hypothesis of the role of non-degradation-linked ubiquitination in NF-kappaB activation...
