DOI: 10.4049/jimmunol.167.6.3164. Disruption of NF-κB Signaling Reveals a Novel Role for NF-κB in the Regulation of TNF-Related Apoptosis-Inducing Ligand Expression

Disruption of NF-κB Signaling Reveals a Novel Role for NF-κB in the Regulation of TNF-Related Apoptosis-Inducing Ligand Expression
10.4049/jimmunol.167.6.3164
Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract
AbstractThe NF-κB family of transcription factors functions broadly in the host control of immunoregulatory gene expression, inflammation, and apoptosis. Using Jurkat T cells engineered to inducibly express a transdominant repressor of IκBα, we examined the role of NF-κB in the regulation of cytokine and apoptotic gene expression. In this T cell model, as well as in primary T lymphocytes, expression of TNF-related apoptosis-inducing ligand (TRAIL) apoptotic signaling protein was dramatically down-regulated by inhibition of NF-κB binding activity. TRAIL acts through membrane death receptors to induce apoptosis of activated T lymphocytes and can be up-regulated by a variety of physiological and pharmacological inducers. However, regulation of TRAIL gene expression has not been defined. Treatment with TCR mimetics (PMA/ionomycin, PHA, and anti-CD3/CD28 Abs) resulted in a rapid increase in the expression of TRAIL mRNA and cell surface TRAIL protein. Induction of the transdominant repressor of IκBα dramatically down-regulated surface expression of TRAIL, indicating an essential role for NF-κB in the regulation of TRAIL. The induced expression of TRAIL was linked to a c-Rel binding site in the proximal TRAIL promoter at position −256 to −265; mutation of this site or an adjacent κB site resulted in a complete loss of the inducibility of the TRAIL promoter. The regulation of TRAIL expression by NF-κB may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis in T lymphocytes.
Bibliography
Baetu, T. M., Kwon, H., Sharma, S., Grandvaux, N., & Hiscott, J. (2001). Disruption of NF-ÎºB Signaling Reveals a Novel Role for NF-ÎºB in the Regulation of TNF-Related Apoptosis-Inducing Ligand Expression. The Journal of Immunology, 167(6), 3164â3173.
Authors 5
Tudor M. Baetu (first)
Hakju Kwon (additional)
Sonia Sharma (additional)
Nathalie Grandvaux (additional)
John Hiscott (additional)
References 70 Referenced 101
Dates
Type	When
Created	11 years, 4 months ago (April 20, 2014, 7:30 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 1:56 p.m.)
Indexed	3 months, 1 week ago (May 18, 2025, 12:04 p.m.)
Issued	23 years, 11 months ago (Sept. 15, 2001)
Published	23 years, 11 months ago (Sept. 15, 2001)
Published Print	23 years, 11 months ago (Sept. 15, 2001)
Funders 0
None
BibTeX
@article{Baetu_2001, title={Disruption of NF-κB Signaling Reveals a Novel Role for NF-κB in the Regulation of TNF-Related Apoptosis-Inducing Ligand Expression}, volume={167}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.167.6.3164}, DOI={10.4049/jimmunol.167.6.3164}, number={6}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Baetu, Tudor M. and Kwon, Hakju and Sharma, Sonia and Grandvaux, Nathalie and Hiscott, John}, year={2001}, month=sep, pages={3164–3173} }
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  "abstract": "<jats:title>Abstract</jats:title><jats:p>The NF-\u03baB family of transcription factors functions broadly in the host control of immunoregulatory gene expression, inflammation, and apoptosis. Using Jurkat T cells engineered to inducibly express a transdominant repressor of I\u03baB\u03b1, we examined the role of NF-\u03baB in the regulation of cytokine and apoptotic gene expression. In this T cell model, as well as in primary T lymphocytes, expression of TNF-related apoptosis-inducing ligand (TRAIL) apoptotic signaling protein was dramatically down-regulated by inhibition of NF-\u03baB binding activity. TRAIL acts through membrane death receptors to induce apoptosis of activated T lymphocytes and can be up-regulated by a variety of physiological and pharmacological inducers. However, regulation of TRAIL gene expression has not been defined. Treatment with TCR mimetics (PMA/ionomycin, PHA, and anti-CD3/CD28 Abs) resulted in a rapid increase in the expression of TRAIL mRNA and cell surface TRAIL protein. Induction of the transdominant repressor of I\u03baB\u03b1 dramatically down-regulated surface expression of TRAIL, indicating an essential role for NF-\u03baB in the regulation of TRAIL. The induced expression of TRAIL was linked to a c-Rel binding site in the proximal TRAIL promoter at position \u2212256 to \u2212265; mutation of this site or an adjacent \u03baB site resulted in a complete loss of the inducibility of the TRAIL promoter. The regulation of TRAIL expression by NF-\u03baB may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis in T lymphocytes.</jats:p>",
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