NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function

Yongqing Wang, Hongjuan Cui, Allen Schroering, Jane L. Ding, William S. Lane, Gaél McGill, David E. Fisher, Han Fei Ding

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Abstract

Nuclear factor-κB (NF-κB) promotes cell survival by upregulating expression of anti-apoptotic genes, a process that is antagonized by inhibitors of κB (IκB) factors1. The only NF-κB family member known to be mutated in human cancer is NF-κB2 p100 (ref. 2), a factor with IκB 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 IκB-like activity. The carboxyl terminus of p100 contains a death domain3 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 IκB-independent apoptotic activity of NF-κB2 p100 and help explain its unique tumour suppressor role.

Original languageEnglish (US)
Pages (from-to)888-893
Number of pages6
JournalNature Cell Biology
Volume4
Issue number11
DOIs
StatePublished - Nov 2002

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Wang, Y., Cui, H., Schroering, A., Ding, J. L., Lane, W. S., McGill, G., Fisher, D. E., & Ding, H. F. (2002). NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function. Nature Cell Biology, 4(11), 888-893. https://doi.org/10.1038/ncb872