Saito, Masumichi; Novak, Urban; Piovan, Erich; Basso, Katia; Sumazin, Pavel; Schneider, Christof; Crespo, Marta; Shen, Qiong; Bhagat, Govind; Califano, Andrea; Chadburn, Amy; Pasqualucci, Laura; Dalla-Favera, Riccardo (2009). BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 106(27), pp. 11294-9. Washington, D.C.: National Academy of Sciences NAS 10.1073/pnas.0903854106
Full text not available from this repository.The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose deregulation by genomic lesions is implicated in the pathogenesis of GC-derived diffuse large B cell lymphoma (DLBCL) and, less frequently, follicular lymphoma (FL). The biological function of BCL6 is only partially understood because no more than a few genes have been functionally characterized as direct targets of BCL6 transrepression activity. Here we report that the anti-apoptotic proto-oncogene BCL2 is a direct target of BCL6 in GC B cells. BCL6 binds to the BCL2 promoter region by interacting with the transcriptional activator Miz1 and suppresses Miz1-induced activation of BCL2 expression. BCL6-mediated suppression of BCL2 is lost in FL and DLBCL, where the 2 proteins are pathologically coexpressed, because of BCL2 chromosomal translocations and other mechanisms, including Miz1 deregulation and somatic mutations in the BCL2 promoter region. These results identify an important function for BCL6 in facilitating apoptosis of GC B cells via suppression of BCL2, and suggest that blocking this pathway is critical for lymphomagenesis.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Novak, Urban |
ISSN: |
0027-8424 |
Publisher: |
National Academy of Sciences NAS |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:11 |
Last Modified: |
05 Dec 2022 14:21 |
Publisher DOI: |
10.1073/pnas.0903854106 |
PubMed ID: |
19549844 |
Web of Science ID: |
000267796100077 |
URI: |
https://boris.unibe.ch/id/eprint/31379 (FactScience: 195873) |
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