Bcl-3 and NF kappa B p50-p50 homodimers act as transcriptional repressors in tolerant CD4(+) T cells
(2004) In Journal of Biological Chemistry 279(9). p.8460-8468- Abstract
- The transcriptional events that control T cell tolerance are still poorly understood. To investigate why tolerant T cells fail to produce interleukin (IL)-2, we analyzed the regulation of NFkappaB-mediated transcription in CD4(+) T cells after tolerance induction in vivo. We demonstrate that a predominance of p50-p50 homodimers binding to the IL-2 promoter kappaB site in tolerant T cells correlated with repression of NFkappaB-driven transcription. Impaired translocation of the p65 subunit in tolerant T cells was a result from reduced activation of IkappaB kinase and poor phosphorylation and degradation of cytosolic IkappaBs. Moreover, tolerant T cells expressed high amounts of the p50 protein. However, the increased expression of p50 could... (More)
- The transcriptional events that control T cell tolerance are still poorly understood. To investigate why tolerant T cells fail to produce interleukin (IL)-2, we analyzed the regulation of NFkappaB-mediated transcription in CD4(+) T cells after tolerance induction in vivo. We demonstrate that a predominance of p50-p50 homodimers binding to the IL-2 promoter kappaB site in tolerant T cells correlated with repression of NFkappaB-driven transcription. Impaired translocation of the p65 subunit in tolerant T cells was a result from reduced activation of IkappaB kinase and poor phosphorylation and degradation of cytosolic IkappaBs. Moreover, tolerant T cells expressed high amounts of the p50 protein. However, the increased expression of p50 could not be explained by activation-induced de novo synthesis of the precursor p105, which was constitutively expressed in tolerant T cells. We also demonstrate the exclusive induction of the IkappaB protein B cell lymphoma 3 (Bcl-3) in tolerant T cells as well as its specific binding to the NFkappaB site. These results suggest that the cellular ratio of NFkappaB dimers, and thus the repression of NFkappaB activity and IL-2 production, are regulated at several levels in tolerant CD4(+) T cells in vivo. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/287099
- author
- Grundstrom, S ; Anderson, Per LU ; Scheipers, P and Sundstedt, A
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 9
- pages
- 8460 - 8468
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000189103300129
- pmid:14668329
- scopus:1542319174
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M312398200
- language
- English
- LU publication?
- yes
- id
- b6ef19f9-4cf6-488e-aa0a-379438a9a4ac (old id 287099)
- date added to LUP
- 2016-04-01 12:20:03
- date last changed
- 2022-04-21 05:59:43
@article{b6ef19f9-4cf6-488e-aa0a-379438a9a4ac, abstract = {{The transcriptional events that control T cell tolerance are still poorly understood. To investigate why tolerant T cells fail to produce interleukin (IL)-2, we analyzed the regulation of NFkappaB-mediated transcription in CD4(+) T cells after tolerance induction in vivo. We demonstrate that a predominance of p50-p50 homodimers binding to the IL-2 promoter kappaB site in tolerant T cells correlated with repression of NFkappaB-driven transcription. Impaired translocation of the p65 subunit in tolerant T cells was a result from reduced activation of IkappaB kinase and poor phosphorylation and degradation of cytosolic IkappaBs. Moreover, tolerant T cells expressed high amounts of the p50 protein. However, the increased expression of p50 could not be explained by activation-induced de novo synthesis of the precursor p105, which was constitutively expressed in tolerant T cells. We also demonstrate the exclusive induction of the IkappaB protein B cell lymphoma 3 (Bcl-3) in tolerant T cells as well as its specific binding to the NFkappaB site. These results suggest that the cellular ratio of NFkappaB dimers, and thus the repression of NFkappaB activity and IL-2 production, are regulated at several levels in tolerant CD4(+) T cells in vivo.}}, author = {{Grundstrom, S and Anderson, Per and Scheipers, P and Sundstedt, A}}, issn = {{1083-351X}}, language = {{eng}}, number = {{9}}, pages = {{8460--8468}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Bcl-3 and NF kappa B p50-p50 homodimers act as transcriptional repressors in tolerant CD4(+) T cells}}, url = {{http://dx.doi.org/10.1074/jbc.M312398200}}, doi = {{10.1074/jbc.M312398200}}, volume = {{279}}, year = {{2004}}, }