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 language | English (US) |
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Pages (from-to) | 888-893 |
Number of pages | 6 |
Journal | Nature Cell Biology |
Volume | 4 |
Issue number | 11 |
DOIs | |
State | Published - Jan 1 2002 |
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ASJC Scopus subject areas
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic function
AU - Wang, Yongqing
AU - Cui, Hongjuan
AU - Schroering, Allen
AU - Ding, Jane L.
AU - Lane, William S.
AU - McGill, Gaél
AU - Fisher, David E.
AU - Ding, Hanfei
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ncb872
DO - 10.1038/ncb872
M3 - Article
C2 - 12389034
AN - SCOPUS:0036850143
VL - 4
SP - 888
EP - 893
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 11
ER -