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

Huifeng Niu, Bihui H. Ye, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

224 Scopus citations

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 languageEnglish (US)
Pages (from-to)1953-1961
Number of pages9
JournalGenes and Development
Volume12
Issue number13
DOIs
StatePublished - Jul 1 1998
Externally publishedYes

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Keywords

  • BCL-6
  • BCR signaling
  • MAP kinase
  • POZ/zinc finger proteins
  • Ubiquitin- proteasome

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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