Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice

Détails

ID Serval
serval:BIB_1E0786F63F72
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice
Périodique
Immunity
Auteur(s)
Yeh  W. C., Shahinian  A., Speiser  D., Kraunus  J., Billia  F., Wakeham  A., de la Pompa  J. L., Ferrick  D., Hum  B., Iscove  N., Ohashi  P., Rothe  M., Goeddel  D. V., Mak  T. W.
ISSN
1074-7613 (Print)
Statut éditorial
Publié
Date de publication
11/1997
Volume
7
Numéro
5
Pages
715-25
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors following TNF stimulation. To investigate the physiological role of TRAF2, we generated TRAF2-deficient mice. traf2-/- mice appeared normal at birth but became progressively runted and died prematurely. Atrophy of the thymus and spleen and depletion of B cell precursors also were observed. Thymocytes and other hematopoietic progenitors were highly sensitive to TNF-induced cell death and serum TNF levels were elevated in these TRAF2-deficient animals. Examination of traf2-/- cells revealed a severe reduction in TNF-mediated JNK/SAPK activation but a mild effect on NF-kappaB activation. These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis.
Mots-clé
Animals Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism Cell Death/*drug effects Cycloheximide/pharmacology Enzyme Activation Female Hematopoietic Stem Cells/cytology JNK Mitogen-Activated Protein Kinases Liver/embryology Male Mice Mice, Inbred C57BL Mice, Knockout *Mitogen-Activated Protein Kinases NF-kappa B/*physiology Protein Synthesis Inhibitors/pharmacology Proteins/*physiology Receptors, Tumor Necrosis Factor/*physiology Signal Transduction TNF Receptor-Associated Factor 2 Tumor Necrosis Factor-alpha/*pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 11:33
Dernière modification de la notice
20/08/2019 12:54
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