Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells.
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Phan RT, Saito M, Kitagawa Y, Means AR, Dalla-Favera R
Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells.
Nat Immunol. 2007 Oct;8(10):1132-9. Epub 2007 Sep 9.
- PubMed ID
- 17828269 [ View in PubMed]
- Abstract
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.