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Inhibition of nuclear factor‐κB activation is essential for membrane‐associated TNF‐α‐induced apoptosis in HL‐60 cells
Author(s) -
Shi Wenfang,
Li Lingyun,
Shi Xu,
Zheng Fang,
Zeng Jingyang,
Jiang Xiaodan,
Gong Feili,
Zhou Muxiang,
Li Zhuoya
Publication year - 2006
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2006.01436.x
Subject(s) - traf2 , chromosomal translocation , cytoplasm , microbiology and biotechnology , apoptosis , downregulation and upregulation , tumor necrosis factor alpha , signal transduction , colocalization , nfkb1 , intracellular , nf κb , biology , chemistry , cancer research , transcription factor , immunology , biochemistry , tumor necrosis factor receptor , gene
The killing of tumour cells that are resistant to soluble TNF‐α (sTNF‐α) by the membrane‐bound form of TNF‐α (mTNF‐α) suggests that different intracellular signalling pathways are involved. We found that mTNF‐α induced apoptosis in HL‐60 cells and failed to cause degradation of inhibitor of kappa B alpha (IκB‐α) and translocation and activation of nuclear factor kappa B (NF‐κB), whereas sTNF‐α failed to induce apoptosis, but lowered cytoplasmic inhibitor of kappa B alpha, induced translocation of NF‐κB to the nucleus and experimentally increased activity of the regulated luciferase. Furthermore, mTNF‐α upregulated the expression of TNF receptor associated factor (TRAF) 1 and failed to induce TRAF1 and TRAF2 membrane translocation, but led to cytoplasmic colocalization. In contrast, sTNF‐α stimulated the expression of TRAF1 and TRAF2, recruiting both molecules onto the cell membrane poststimulation. These results suggest that the increased susceptibility of HL‐60 cells to mTNF‐α may be due to the failure of TRAF2 membrane translocation caused by the upregulation of TRAF1 expression and formation of a TRAF1/TRAF2 complex in the cytoplasm, thereby inhibiting NF‐κB activation and inducing apoptosis.