Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-κB
Author: ["Rajani Ravi","Gauri. C. Bedi","Laura W. Engstrom","Qinwen Zeng","Bijoyesh Mookerjee","Céline Gélinas","Ephraim J. Fuchs","Atul Bedi"]
Publication: Nature Cell Biology
CITE.CC academic search helps you expand the influence of your papers.
Abstract
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.
Cite this article
Ravi, R., Bedi, G., Engstrom, L. et al. Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-κB. Nat Cell Biol 3, 409–416 (2001). https://doi.org/10.1038/35070096
