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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2007-9-5
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pubmed:abstractText |
The BCL6 proto-oncogene encodes a transcriptional repressor necessary for the development of germinal centers (GCs) and directly implicated in lymphomagenesis. Post-GC development of B cells requires BCL6 downregulation, while its constitutive expression caused by chromosomal translocations leads to diffuse large B cell lymphoma (DLBCL). Herein we identify a signaling pathway that downregulates BCL6 expression in normal GC B cells and is blocked in a subset of DLBCL due to alterations in the BCL6 gene. Activation of the CD40 receptor leads to NF-kappaB-mediated induction of the IRF4 transcription factor, which, in turn, represses BCL6 expression by binding to its promoter region. A subset of DLBCL displays chromosomal translocations or mutations that disrupt the IRF4-responsive region in the BCL6 promoter and block its downregulation by CD40 signaling.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1535-6108
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
280-92
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17785208-Antigens, CD40,
pubmed-meshheading:17785208-B-Lymphocytes,
pubmed-meshheading:17785208-DNA-Binding Proteins,
pubmed-meshheading:17785208-Down-Regulation,
pubmed-meshheading:17785208-Germinal Center,
pubmed-meshheading:17785208-Interferon Regulatory Factors,
pubmed-meshheading:17785208-Lymphoma, B-Cell,
pubmed-meshheading:17785208-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:17785208-Mutation,
pubmed-meshheading:17785208-NF-kappa B,
pubmed-meshheading:17785208-Signal Transduction,
pubmed-meshheading:17785208-Transcription, Genetic,
pubmed-meshheading:17785208-Translocation, Genetic
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pubmed:year |
2007
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pubmed:articleTitle |
A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma.
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pubmed:affiliation |
Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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