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CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/ref-1-dependent redox mechanism

Merluzzi, S; Moretti, M; Altamura, S; Zwollo, P; Sigvardsson, Mikael LU ; Vitale, G and Pucillo, C (2004) In Journal of Biological Chemistry 279(3). p.1777-1786
Abstract
CD40 is a member of the growing tumor necrosis factor receptor family that has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154, mainly expressed on activated T cells, stimulates B cell proliferation, differentiation, isotype switching, up-regulation of surface molecules contributing to antigen presentation, development of the germinal center, and the humoral memory response. In this study we demonstrate that the redox factor APE/Ref-1 acts as a key signaling intermediate in response to CD40-mediated B cell activation. The transcription factors Pax5a or BSAP ( B cell lineage-specific activator protein) and EBF ( early B cell factor) are constitutively expressed in spleen B... (More)
CD40 is a member of the growing tumor necrosis factor receptor family that has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154, mainly expressed on activated T cells, stimulates B cell proliferation, differentiation, isotype switching, up-regulation of surface molecules contributing to antigen presentation, development of the germinal center, and the humoral memory response. In this study we demonstrate that the redox factor APE/Ref-1 acts as a key signaling intermediate in response to CD40-mediated B cell activation. The transcription factors Pax5a or BSAP ( B cell lineage-specific activator protein) and EBF ( early B cell factor) are constitutively expressed in spleen B cells and CD40 cross-linking induces increases in Pax5a and EBF binding activity compared with nonstimulated B cells. We show that upon CD40 antibody-mediated cross-linking, APE/Ref-1 translocates from the cytoplasm to the nucleus of activated B cells, where it modulates the DNA binding activity of both Pax5a and EBF. Moreover, we show that the repression of APE/Ref-1 protein production is able to block CD40-mediated Pax5a activation. We also provide evidence that APE/Ref-1 can modulate the cooperative activation of the blk promoter operated by Pax5a and EBF and that APE/Ref-1 might directly regulate EBF functional activity. Finally, we show that the interaction between Pax5a and EBF enhances EBF binding activity to its consensus sequence, suggesting that Pax5a can physically interact with EBF and modulate its DNA binding activity. (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
3
pages
1777 - 1786
publisher
ASBMB
external identifiers
  • wos:000188005700027
  • pmid:14594818
  • scopus:0347717886
ISSN
1083-351X
DOI
10.1074/jbc.M305418200
language
English
LU publication?
yes
id
5e349b87-073d-4172-b9f7-288c5dc63e48 (old id 290070)
date added to LUP
2007-10-28 14:51:10
date last changed
2017-07-23 03:38:35
@article{5e349b87-073d-4172-b9f7-288c5dc63e48,
  abstract     = {CD40 is a member of the growing tumor necrosis factor receptor family that has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154, mainly expressed on activated T cells, stimulates B cell proliferation, differentiation, isotype switching, up-regulation of surface molecules contributing to antigen presentation, development of the germinal center, and the humoral memory response. In this study we demonstrate that the redox factor APE/Ref-1 acts as a key signaling intermediate in response to CD40-mediated B cell activation. The transcription factors Pax5a or BSAP ( B cell lineage-specific activator protein) and EBF ( early B cell factor) are constitutively expressed in spleen B cells and CD40 cross-linking induces increases in Pax5a and EBF binding activity compared with nonstimulated B cells. We show that upon CD40 antibody-mediated cross-linking, APE/Ref-1 translocates from the cytoplasm to the nucleus of activated B cells, where it modulates the DNA binding activity of both Pax5a and EBF. Moreover, we show that the repression of APE/Ref-1 protein production is able to block CD40-mediated Pax5a activation. We also provide evidence that APE/Ref-1 can modulate the cooperative activation of the blk promoter operated by Pax5a and EBF and that APE/Ref-1 might directly regulate EBF functional activity. Finally, we show that the interaction between Pax5a and EBF enhances EBF binding activity to its consensus sequence, suggesting that Pax5a can physically interact with EBF and modulate its DNA binding activity.},
  author       = {Merluzzi, S and Moretti, M and Altamura, S and Zwollo, P and Sigvardsson, Mikael and Vitale, G and Pucillo, C},
  issn         = {1083-351X},
  language     = {eng},
  number       = {3},
  pages        = {1777--1786},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/ref-1-dependent redox mechanism},
  url          = {http://dx.doi.org/10.1074/jbc.M305418200},
  volume       = {279},
  year         = {2004},
}