Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Phan, RT; Saito, M; Kitagawa, Y; Means, AR; Dalla-Favera, R
Published Date
- October 2007
Published In
Volume / Issue
- 8 / 10
Start / End Page
- 1132 - 1139
PubMed ID
- 17828269
Pubmed Central ID
- 17828269
International Standard Serial Number (ISSN)
- 1529-2908
Digital Object Identifier (DOI)
- 10.1038/ni1508
Language
- eng
Conference Location
- United States