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

Published

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