Document Detail


NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells.
MedLine Citation:
PMID:  18663224     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BAFF-R-dependent activation of the alternative NF-kappaB pathway plays an essential role in mature B cell survival. Mutations leading to overexpression of NIK and deletion of the TRAF3 gene are implicated in human multiple myeloma. We show that overexpression of NIK in mouse B lymphocytes amplifies alternative NF-kappaB activation and peripheral B cell numbers in a BAFF-R-dependent manner, whereas uncoupling NIK from TRAF3-mediated control causes maximal p100 processing and dramatic hyperplasia of BAFF-R-independent B cells. NIK controls alternative NF-kappaB signaling by increasing the protein levels of its negative regulator TRAF3 in a dose-dependent fashion. This mechanism keeps NIK protein levels below detection even when they cause B cell hyperplasia, so that contributions of NIK to B cell pathologies can easily be overlooked.
Authors:
Yoshiteru Sasaki; Dinis P Calado; Emmanuel Derudder; Baochun Zhang; Yuri Shimizu; Fabienne Mackay; Shin-ichi Nishikawa; Klaus Rajewsky; Marc Schmidt-Supprian
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-28
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-06     Completed Date:  2008-09-25     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10883-8     Citation Subset:  IM    
Affiliation:
Immune Disease Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. yoshisasaki@cdb.riken.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Cell Activating Factor / metabolism*
B-Cell Activation Factor Receptor / metabolism
B-Lymphocytes / immunology,  metabolism*
Blotting, Northern
Blotting, Western
Cell Proliferation
Cell Survival / immunology
Flow Cytometry
Gene Expression Regulation / immunology*
Immunohistochemistry
Mice
NF-kappa B / metabolism
Protein Structure, Tertiary
Protein-Serine-Threonine Kinases / metabolism*
Signal Transduction / immunology*
TNF Receptor-Associated Factor 3 / metabolism
Grant Support
ID/Acronym/Agency:
AI054636/AI/NIAID NIH HHS; AI057947/AI/NIAID NIH HHS; CA92625/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/B-Cell Activating Factor; 0/B-Cell Activation Factor Receptor; 0/NF-kappa B; 0/TNF Receptor-Associated Factor 3; 0/Tnfrsf13c protein, mouse; 0/Tnfsf13b protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.25/NF-kappa B kinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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