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PMID: 9649500 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Genes & development ·Vol. 12 ·No. 13 ·1998-07-01 ·Pages 1953-61

Niu H, Ye BH, Dalla-Favera R

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.

MeSH Terms
B-Lymphocytes/enzymology,metabolism Burkitt Lymphoma Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Cysteine Endopeptidases/metabolism DNA-Binding Proteins/metabolism Humans Kidney Multienzyme Complexes/metabolism Phosphorylation Proteasome Endopeptidase Complex Proto-Oncogene Mas Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-6 Receptors, Antigen, B-Cell/physiology Signal Transduction/immunology Transcription Factors/metabolism Tumor Cells, Cultured Ubiquitins/metabolism
Chemicals
DNA-Binding Proteins MAS1 protein, human Multienzyme Complexes Proto-Oncogene Mas Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-6 Receptors, Antigen, B-Cell Transcription Factors Ubiquitins Calcium-Calmodulin-Dependent Protein Kinases Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Niu H
Departments of Pathology and Genetics and Development, Columbia University, New York, New York 10032 USA.
Ye B H
Dalla-Favera R
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.13.1953
Published
1998-07-01
Pages
1953-61
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316953
Subset
IM
Grants
NCI NIH HHS · CA-37295 · United States
External Links
PubMed source DOI: 10.1101/gad.12.13.1953 PMC Full Text View journal details
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