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, Hanfei Ding

Research output: Contribution to journalArticle

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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 - Jan 1 2002

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Apoptosis Regulatory Proteins
Caspase 8
Neoplasms
Apoptosis
Death Domain Receptors
Cell Survival
Cell Death
Ligands
Genes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Wang, Y., Cui, H., Schroering, A., Ding, J. L., Lane, W. S., McGill, G., ... Ding, H. (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

NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function. / Wang, Yongqing; Cui, Hongjuan; Schroering, Allen; Ding, Jane L.; Lane, William S.; McGill, Gaél; Fisher, David E.; Ding, Hanfei.

In: Nature Cell Biology, Vol. 4, No. 11, 01.01.2002, p. 888-893.

Research output: Contribution to journalArticle

Wang, Y, Cui, H, Schroering, A, Ding, JL, Lane, WS, McGill, G, Fisher, DE & Ding, H 2002, 'NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function', Nature Cell Biology, vol. 4, no. 11, pp. 888-893. https://doi.org/10.1038/ncb872
Wang Y, Cui H, Schroering A, Ding JL, Lane WS, McGill G et al. NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function. Nature Cell Biology. 2002 Jan 1;4(11):888-893. https://doi.org/10.1038/ncb872
Wang, Yongqing ; Cui, Hongjuan ; Schroering, Allen ; Ding, Jane L. ; Lane, William S. ; McGill, Gaél ; Fisher, David E. ; Ding, Hanfei. / NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function. In: Nature Cell Biology. 2002 ; Vol. 4, No. 11. pp. 888-893.
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