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PMID: 12407182 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 23 ·2002-11-12 ·Pages 15018-23

Wang X, Li Z, Naganuma A, Ye BH

Abstract

Thirty to forty percent of diffuse large B cell lymphomas (DLBCL) carry BCL-6 translocations that disrupt its 5' regulatory region. This same region is also subject to somatic hypermutations, although only a small fraction of these mutations have a detectable effect on transcription. Here, we show that transcription of the BCL-6 gene is negatively self-regulated in multiple cell types. This mechanism operates by means of the interaction of two BCL-6-binding sites within exon 1 of the gene and the BCL-6 protein itself, which is a potent transcription repressor. Because the DLBCL-associated "activating mutations" specifically target these exon 1 binding sites, and because the entire exon 1 is usually removed in the BCL-6-translocated tumors, this autoregulation is bypassed in 30-40% of all DLBCL cases. Our results not only demonstrate an important mechanism governing the expression of BCL-6, but also explain how BCL-6 is deregulated in a large number of DLBCL patients, providing a better understanding of BCL-6-related lymphomagenesis.

MeSH Terms
3T3 Cells Animals Base Sequence Chromatin/genetics,immunology DNA Primers DNA-Binding Proteins/deficiency,genetics,physiology Gene Expression Regulation, Neoplastic Genes, Reporter Homeostasis Humans Lymphoma, B-Cell/genetics,immunology Mice Mice, Knockout Molecular Sequence Data Proto-Oncogene Proteins/deficiency,genetics,physiology Proto-Oncogene Proteins c-bcl-6 RNA, Messenger/genetics Reverse Transcriptase Polymerase Chain Reaction Transcription Factors/deficiency,genetics,physiology Transfection Translocation, Genetic
Chemicals
Chromatin DNA Primers DNA-Binding Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-6 RNA, Messenger Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wang Xing
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Li Zhiping
Naganuma Akira
Ye B Hilda
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43 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.232581199
Published
2002-11-12
Epub
2002-00-29
Pages
15018-23
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC137537
Subset
IM
Grants
NCI NIH HHS · R01 CA085573 · United States
NCI NIH HHS · R01 CA85573 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1073/pnas.232581199 PMC Full Text View journal details
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