CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/ref-1-dependent redox mechanism
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/290070
- author
- Merluzzi, S ; Moretti, M ; Altamura, S ; Zwollo, P ; Sigvardsson, Mikael LU ; Vitale, G and Pucillo, C
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 3
- pages
- 1777 - 1786
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000188005700027
- pmid:14594818
- scopus:0347717886
- pmid:14594818
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M305418200
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012)
- id
- 5e349b87-073d-4172-b9f7-288c5dc63e48 (old id 290070)
- date added to LUP
- 2016-04-01 11:45:05
- date last changed
- 2022-04-05 04:33:39
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M305418200}},
volume = {{279}},
year = {{2004}},
}