|NF-kappa B2 p100 is a pro-apoptotic protein with anti-oncogenic function.|
|PMID: 12389034 Owner: NLM Status: MEDLINE|
|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.|
|Yongqing Wang; Hongjuan Cui; Allen Schroering; Jane L Ding; William S Lane; Gaël McGill; David E Fisher; Han-Fei Ding|
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|Type: Journal Article; Research Support, U.S. Gov't, P.H.S.|
|Title: Nature cell biology Volume: 4 ISSN: 1465-7392 ISO Abbreviation: Nat. Cell Biol. Publication Date: 2002 Nov|
|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|
|Languages: eng Pagination: 888-93 Citation Subset: IM|
|Department of Biochemistry and Molecular Biology, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Caspases / metabolism
Cell Line, Tumor
Cycloheximide / pharmacology
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Gene Transfer Techniques
Genes, Tumor Suppressor
NF-kappa B / metabolism, physiology*
NF-kappa B p52 Subunit
NIH 3T3 Cells
Plasmids / metabolism
Protein Structure, Tertiary
Retroviridae / genetics
|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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