Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells.

Antigen-specific B cells are selected in germinal centers, the structure in which these cells proliferate while accomplishing genome-remodeling processes such as class-switch recombination and somatic hypermutation. These events are associated with considerable genotoxic stress, which cells tolerate through suppression of DNA-damage responses by Bcl-6, a transcription factor required for the ...
formation of germinal centers. Here we show that the expression of Bcl-6 is regulated by DNA damage through a signaling pathway that promotes Bcl-6 degradation. After DNA damage accumulated, the kinase ATM promoted Bcl-6 phosphorylation, leading to its interaction with the isomerase Pin1 and its degradation by the ubiquitin-proteasome system. Because Bcl-6 is required for the maintenance of germinal centers, our findings suggest that the extent of genotoxic stress controls the fate of germinal center B cells by means of Bcl-6.
Mesh Terms:
B-Lymphocytes, Cell Cycle Proteins, DNA Damage, DNA-Binding Proteins, Etoposide, Gene Expression Regulation, Germinal Center, Humans, Peptidylprolyl Isomerase, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogenes, Tumor Suppressor Proteins
Nat. Immunol.
Date: Oct. 01, 2007
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