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Vol. 12, No. 13, pp. 1953-1961, July 1, 1998
Departments of Pathology and Genetics and Development, Columbia
University, New York, New York 10032 USA
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.
[Key Words: BCL-6; BCR signaling; MAP kinase; POZ/zinc finger proteins; ubiquitin-proteasome]
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