GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:14594818

From GONUTS
Jump to: navigation, search
Citation

Merluzzi, S, Moretti, M, Altamura, S, Zwollo, P, Sigvardsson, M, Vitale, G and Pucillo, C (2004) CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/Ref-1-dependent redox mechanism. J. Biol. Chem. 279:1777-86

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.

Links

PubMed Online version:10.1074/jbc.M305418200

Keywords

Active Transport, Cell Nucleus; Adaptor Proteins, Signal Transducing; Animals; Antigens, CD40/physiology; B-Cell-Specific Activator Protein; Carrier Proteins/genetics; DNA/metabolism; DNA-(Apurinic or Apyrimidinic Site) Lyase/physiology; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Female; Mice; Mice, Inbred BALB C; Mitochondrial Proteins; Oxidation-Reduction; Promoter Regions, Genetic; Trans-Activators/chemistry; Trans-Activators/metabolism; Transcription Factors/chemistry; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

See Help:References for how to manage references in GONUTS.