Genomes and Genes
- The NF-kappaB signaling pathway in human genetic diseasesGilles Courtois
INSERM U697, Pavillon Bazin, Hopital Saint Louis, 1, avenue Claude Vellefaux, 75010, Paris, France
Cell Mol Life Sci 62:1682-91. 2005..In this review, a summary of the pathophysiological consequences of impaired NF-kappaB activation in humans is provided with respect to the functions of the molecules which are mutated...
- NF-kappaB-related genetic diseasesG Courtois
INSERM U697, Pavillon Bazin, Hopital Saint Louis, Paris, France
Cell Death Differ 13:843-51. 2006..In addition, the identified mutations will help understanding at the molecular level how NF-kappaB is activated in response to cell stimulation...
- Tumor suppressor CYLD: negative regulation of NF-kappaB signaling and moreG Courtois
INSERM U697, Pavillon Bazin, Hopital Saint Louis, 1 avenue Claude Vellefaux, Paris, France
Cell Mol Life Sci 65:1123-32. 2008....
- Inhibition of IkappaB kinase subunit 2 in cutaneous T-cell lymphoma down-regulates nuclear factor-kappaB constitutive activation, induces cell death, and potentiates the apoptotic response to antineoplastic chemotherapeutic agentsAurore Sors
Unité Institut National de la Sante et de la Recherche Medicale U697 and Department of Dermatology 1, Hopital Saint Louis, AP HP, Universite Paris 7, Paris, France
Clin Cancer Res 14:901-11. 2008..We investigated in vitro the effects on CTCL survival and chemoresistance of a specific inhibition of IkappaB kinase subunit 2 (IKK2)...
- Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphomaElodie Bégué
Centre de Recherche sur la Peau, Universite Paris Diderot, Hopital Saint Louis, Paris, France
Blood 120:143-54. 2012..In conclusion, T-plastin is a marker restricted to malignant lymphocytes from SS patients and plays a role for cell survival and migration. This opens new strategies for the treatment of SS advanced stages...
- Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmentiHélène Sebban-Benin
INSERM U697, Pavilion Bazin, Hopital Saint Louis, Paris, France
Hum Mol Genet 16:2805-15. 2007..These findings indicate that post-translational modification of NEMO through K63-linked polyubiquitination is a key event in IKK activation and that perturbation of this step may cause human pathophysiology...
- NF-kappaB and inflammation in genetic diseaseHélène Sebban
INSERM U697, Pavillon Bazin, Hopital Saint Louis, 1, avenue Claude Vellefaux, 75010 Paris, France
Biochem Pharmacol 72:1153-60. 2006....
- 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...
- Posttranslational modifications of NEMO and its partners in NF-kappaB signalingHélène Sebban
INSERM U697, Hopital Saint Louis, Paris 75010, France
Trends Cell Biol 16:569-77. 2006....
- A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide- and tumor necrosis factor-mediated NF-kappa B activationEmilie Vinolo
Unité de Régulation Enzymatique des Activités Cellulaires, CNRS URA 2185, Paris, France
J Biol Chem 281:6334-48. 2006..Altogether, our findings provide understanding as to how a single point mutation in NEMO leads to the observed EDA-ID phenotype in relation to the NEMO-dependent mechanism of IKK activation...
- Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his motherSophie Dupuis-Girod
, , Paris, France
Pediatrics 109:e97. 2002..In contrast, loss-of-function mutations and hypomorphic mutations may cause IP in females...
- IKK regulation and human geneticsGilles Courtois
INSERM U781, Hopital Necker Enfants Malades, Paris, France
Curr Top Microbiol Immunol 349:73-95. 2011....
- "Without Ub I am nothing": NEMO as a multifunctional player in ubiquitin-mediated control of NF-kappaB activationJérémie Gautheron
INSERM U781, Tour Lavoisier, Hôpital Necker Enfants Malades and Université Paris Descartes, 149, rue de Sevres, 75015, Paris, France
Cell Mol Life Sci 67:3101-13. 2010....
- Down-regulating constitutive activation of the NF-kappaB canonical pathway overcomes the resistance of cutaneous T-cell lymphoma to apoptosisAurore Sors
INSERM U697, Institut de Recherche sur la Peau, Pavillon Bazin, Hopital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Blood 107:2354-63. 2006....
- NF-kappaB in skin homeostasisGilles Courtois
INSERM U697, Hopital Saint-Louis, Institut de Recherche sur la Peau, 1 avenue Claude Vellefaux, 75010 Paris, France
Exp Dermatol 14:781-2. 2005
- Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activationS Yamaoka
Unité de Biologie Moléculaire de l Expression Génique, URA 1773 CNRS, Institut Pasteur, Paris, France
Cell 93:1231-40. 1998..3E2, in which the protein is also absent, allowing us to demonstrate that this factor is required not only for Tax but also for LPS, PMA, and IL-1 stimulation of NF-kappaB activity...
- Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) ConsortiumA Smahi
Department of Genetics, Unité de Recherches sur les Handicaps Génétiques de l Enfant INSERMU 393, Hopital Necker Enfants Malades, Paris, France
Nature 405:466-72. 2000..Here we show that most cases of IP are due to mutations of this locus and that a new genomic rearrangement accounts for 80% of new mutations. As a consequence, NF-kappaB activation is defective in IP cells...
- X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signalingR Doffinger
Laboratoire de Genetique Humaine des Maladies Infectieuses, Faculte de Medecine Necker Enfants Malades, Paris, France
Nat Genet 27:277-85. 2001..We thus report for the first time that impaired but not abolished NF-kappaB signaling in humans results in two related syndromes that associate specific developmental and immunological defects...
- Mutations in the NF-kappaB signaling pathway: implications for human diseaseG Courtois
INSERM U697, , Paris, France
Oncogene 25:6831-43. 2006..In addition, human genetic diseases are briefly described wherein mutations affect protein modifiers or transducers of NF-kappaB signaling or disrupt NF-kappaB-binding sites in promoters/enhancers...
- Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locusE Bal
INSERM U781 et Département de Génétique, Hopital Necker Enfants Malades, Paris, France
Hum Mutat 28:703-9. 2007..Our results confirm that NF-kB activation is impaired in EDA and support the role of EDARADD DD as a downstream effector of EDAR signaling...
- The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitinationAndrew Kovalenko
Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
Nature 424:801-5. 2003..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology...
- Post-induction, stimulus-specific regulation of tumor necrosis factor mRNA expressionAlla V Tsytsykova
CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 282:11629-38. 2007....
- The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromesAsma Smahi
Département de Génétique et Unité de Recherches sur les Handicaps Génétiques de l Enfant INSERM UR 393, Hopital Necker, 149 rue de Sevres, 75743 Paris Cedex 15, France
Hum Mol Genet 11:2371-5. 2002..Unravelling the molecular bases of other forms of EDA not associated with mutations in NEMO will possibly implicate other components of the NF-kappaB signalling pathway...
- [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...
- Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activationFrancesca Fusco
Institute of Genetics and Biophysics, Adriano Buzzati Traverso CR, Naples, Italy
Hum Mol Genet 13:1763-73. 2004..Indeed, 64% of our patients have extremely skewed X-inactivation pattern (>/=80 : 20). Overall IP pathogenesis thus depends on a combination of X-inactivation and protein domain that recruit upstream factors and activate NF-kappaB...
- 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...
- TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2Manolis Pasparakis
Institute for Genetics, University of Cologne, Weyertal 121, D 50931 Cologne, Germany
Nature 417:861-6. 2002..Our results suggest that the critical function of IKK2-mediated NF-kappa B activity in epidermal keratinocytes is to regulate mechanisms that maintain the immune homeostasis of the skin...
- 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...
- Yersinia outer protein P suppresses TGF-beta-activated kinase-1 activity to impair innate immune signaling in Yersinia enterocolitica-infected cellsRudolf Haase
Max von Pettenkofer Institute for Hygiene and Medical Microbiology, Munich, Germany
J Immunol 175:8209-17. 2005....
- Two carboxyl-terminal activation regions of Epstein-Barr virus latent membrane protein 1 activate NF-kappaB through distinct signaling pathways in fibroblast cell linesNaohito Saito
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8519, Japan
J Biol Chem 278:46565-75. 2003..Our results thus help clarify how two functional domains of LMP1 persistently activate NF-kappaB through distinct signaling pathways...
- Mature T cells depend on signaling through the IKK complexMarc Schmidt-Supprian
Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Immunity 19:377-89. 2003..Thus, IKK-induced NF-kappaB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development...
- 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...