Document Detail


NF-kappa B2 p100 is a pro-apoptotic protein with anti-oncogenic function.
MedLine Citation:
PMID:  12389034     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nuclear factor-kappa B (NF-kappa B) promotes cell survival by upregulating expression of anti-apoptotic genes, a process that is antagonized by inhibitors of kappa B (I kappa B) factors. The only NF-kappa B family member known to be mutated in human cancer is NF-kappa B2 p100 (ref. 2), a factor with I kappa B activity. Here, we report the isolation from irradiated mouse tumour cells of a complex that induces caspase-8 activity in cell-free assays and identify p100 as an essential component of this complex. Expression of p100 profoundly sensitizes cells to death-receptor-mediated apoptosis through a pathway that is independent of I kappa B-like activity. The carboxyl terminus of p100 contains a death domain that is absent from all known tumour-derived mutants. This death domain mediates recruitment of p100 into death machinery complexes after ligand stimulation and is essential for p100's pro-apoptotic activity. p100 also sensitizes NIH3T3 cells to apoptosis triggered by oncogenic Ras, resulting in a marked inhibition of transformation that is rescued by suppression of endogenous caspase-8. These observations thus identify an I kappa B-independent apoptotic activity of NF-kappa B2 p100 and help explain its unique tumour suppressor role.
Authors:
Yongqing Wang; Hongjuan Cui; Allen Schroering; Jane L Ding; William S Lane; Gaël McGill; David E Fisher; Han-Fei Ding
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature cell biology     Volume:  4     ISSN:  1465-7392     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-04     Completed Date:  2004-04-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  888-93     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Caspase 8
Caspases / metabolism
Cell Death
Cell Line, Tumor
Cell Survival
Cell-Free System
Colorimetry
Cycloheximide / pharmacology
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Enzyme Activation
Gene Transfer Techniques
Genes, Tumor Suppressor
Humans
Immunoblotting
Mass Spectrometry
Mice
Mutation
NF-kappa B / metabolism,  physiology*
NF-kappa B p52 Subunit
NIH 3T3 Cells
Plasmids / metabolism
Protein Binding
Protein Structure, Tertiary
Retroviridae / genetics
Time Factors
Transfection
Up-Regulation
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/NF-kappa B p52 Subunit; 66-81-9/Cycloheximide; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases

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


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