Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor

H Niu, HY Bihui, R Dalla-Favera - Genes & development, 1998 - genesdev.cshlp.org
H Niu, HY Bihui, R Dalla-Favera
Genes & development, 1998genesdev.cshlp.org
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 …
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.
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