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Bcl-3 and NF kappa B p50-p50 homodimers act as transcriptional repressors in tolerant CD4(+) T cells

Grundstrom, S; Anderson, Per LU ; Scheipers, P and Sundstedt, A (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)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
9
pages
8460 - 8468
publisher
ASBMB
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
2007-10-29 09:41:05
date last changed
2017-09-17 05:08:45
@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    = {ASBMB},
  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},
  volume       = {279},
  year         = {2004},
}