Caspase cleavage product lacking amino-terminus of IκBα sensitizes resistant cells to TNF-α and TRAIL-induced apoptosis

Ki Woo Kim, Byung Ju Kim, Chul Woong Chung, Dong Gyu Jo, In Ki Kim, You Hyun Song, Yun Kyung Kwon, Ha Na Woo, Yong Keun Jung

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


In response to a diverse array of signals, IκBα is targeted for phosphorylation-dependent degradation by the proteasome, thereby activating NF-κB. Here we demonstrate a role of the cleavage product of IκBα in various death signals. During apoptosis of NIH3T3, Jurkat, Rat-1, and L929 cells exposed to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas, serum deprivation, or TNF-α, respectively, IκBα was cleaved in a caspase-dependent manner. In vitro and in vivo cleavage assays and site-directed mutagenesis showed that caspase-3 cleaved IκBα between Asp31 and Ser32. Expression of the cleavage product lacking amino-terminus (1-31), ΔIκBα, sensitized otherwise resistant NIH3T3 fibroblast cells to apoptosis induced by TNF-α or TRAIL, and HeLa tumor cells to TNF-α. ΔIκBα was more pro-apoptotic compared to wild type or cleavage-resistant (D31E)IκBα mutant and the sensitization elicited by ΔIκBα was as effective as that by the dominant negative mutant, (S32,36A)IκBα in NIH3T3 cells. ΔIκBα suppressed the transactivation of NF-κB induced by TNF-α or TRAIL, as reflected by luciferase-reporter activity. Conversely, expression of the p65 subunit of NF-κB suppressed TNF-α-, TRAIL-, and serum deprivation-induced cell death. On the contrary, ΔIκBα was less effective at increasing the death rate of HeLa cells that were already sensitive to death signals including TRAIL, etoposide, or taxol. These results suggest that ΔIκBα generated by various death signals sensitizes cells to apoptosis by suppressing NF-κB activity.

Original languageEnglish
Pages (from-to)334-345
Number of pages12
JournalJournal of Cellular Biochemistry
Issue number2
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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