Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-κB

Rajani Ravi, Gauri C. Bedi, Laura W. Engstrom, Qinwen Zeng, Bijoyesh Mookerjee, Céline Gélinas, Ephraim J. Fuchs, Atul Bedi

Research output: Contribution to journalArticlepeer-review


TRAIL (tumour-necrosis factor-related apoptosis ligand or Apo2L) triggers apoptosis through engagement of the death receptors TRAIL-R1 (also known as DR4) and TRAIL-R2 (DR5). Here we show that the c-Rel subunit of the transcription factor NF-κB induces expression of TRAIL-R1 and TRAIL-R2; conversely, a transdominant mutant of the inhibitory protein IκBα or a transactivation-deficient mutant of c-Rel reduces expression of either death receptor. Whereas NF-κB promotes death receptor expression, cytokine-mediated activation of the RelA subunit of NF-κB also increases expression of the apoptosis inhibitor, Bcl-xL, and protects cells from TRAIL. Inhibition of NF-κB by blocking activation of the IκB kinase complex reduces Bcl-xL expression and sensitizes tumour cells to TRAIL-induced apoptosis. The ability to induce death receptors or Bcl-xL may explain the dual roles of NF-κB as a mediator or inhibitor of cell death during immune and stress responses.

Original languageEnglish (US)
Pages (from-to)409-416
Number of pages8
JournalNature cell biology
Issue number4
StatePublished - 2001

ASJC Scopus subject areas

  • Cell Biology


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