Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

Beverly W Baron; Nancy Zeleznik-Le; Miriam J Baron; Catherine Theisler; Dezheng Huo; Matthew D Krasowski; Michael J Thirman; Rebecca M Baron; Joseph M Baron

doi:10.1073/pnas.0701770104

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Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

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Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

Beverly W Baron, Nancy Zeleznik-Le, Miriam J Baron, Catherine Theisler, Dezheng Huo, Matthew D Krasowski, Michael J Thirman, Rebecca M Baron and Joseph M Baron

Proceedings of the National Academy of Sciences - PNAS, Vol.104(18), pp.7449-7454

05/01/2007

DOI: 10.1073/pnas.0701770104

PMCID: PMC1863460

PMID: 17468402

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Abstract

The human BCL6 gene on chromosome 3 band q27, which encodes a transcriptional repressor, is implicated in the pathogenesis of human lymphomas, especially the diffuse large B-cell type. We previously identified the human PDCD2 (programmed cell death-2) gene as a target of BCL6 repression. PDCD2 encodes a protein that is expressed in many human tissues, including lymphocytes, and is known to interact with corepressor complexes. We now show that BCL6 can bind directly to the PDCD2 promoter, repressing its transcription. Knockdown of endogenous BCL6 in a human B cell lymphoma line by introduction of small interfering RNA duplexes increases PDCD2 protein expression. Furthermore, there is an inverse relationship between the expression levels of the BCL6 and PDCD2 proteins in the lymphoid tissues of mice overexpressing human BCL6 (high BCL6 levels, minimal PDCD2) and controls (minimal BCL6, high PDCD2) as well as in tissues examined from some human B and T cell lymphomas. These data confirm PDCD2 as a target of BCL6 and support the concept that repression of PDCD2 by BCL6 is likely important in the pathogenesis of certain human lymphomas.

Biological Sciences

human lymphomas

target of BCL6

Details

Title: Subtitle: Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas
Creators: Beverly W Baron - Departments of Pathology
Nancy Zeleznik-Le - Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153; and
Miriam J Baron - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Catherine Theisler - Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153; and
Dezheng Huo - Health Studies, and
Matthew D Krasowski - Departments of Pathology
Michael J Thirman - Medicine, University of Chicago, Chicago, IL 60637
Rebecca M Baron - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Joseph M Baron - Medicine, University of Chicago, Chicago, IL 60637
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.104(18), pp.7449-7454
DOI: 10.1073/pnas.0701770104
PMID: 17468402
PMCID: PMC1863460
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 05/01/2007
Academic Unit: Pathology
Record Identifier: 9984047741902771

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