Abstract
The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in the pathogenesis of B-cell lymphoma. The signals regulating bcl-6 expression are not known. Here we show that antigen receptor activation leads to BCL-6 phosphorylation by mitogen-activated protein kinase (MAPK). Phosphorylation, in turn, targets BCL-6 for rapid degradation by the ubiquitin/proteasome pathway. These findings indicate that BCL-6 expression is directly controlled by the antigen receptor via MAPK activation. This signaling pathway may be crucial for the control of B-cell differentiation and antibody response and has implications for the regulation of other POZ/zinc finger transcription factors in other tissues.
Original language | English (US) |
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Pages (from-to) | 1953-1961 |
Number of pages | 9 |
Journal | Genes and Development |
Volume | 12 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 1998 |
Externally published | Yes |
Keywords
- BCL-6
- BCR signaling
- MAP kinase
- POZ/zinc finger proteins
- Ubiquitin- proteasome
ASJC Scopus subject areas
- Genetics
- Developmental Biology