Repression of AP-1 function: A mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene

Farha H. Vasanwala, Saritha Kusam, Lisa M. Toney, Alexander Dent

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Abstract

The B cell lymphoma-6 (BCL-6) transcriptional repressor protein is an important regulator of B cell differentiation and is strongly implicated in the development of B cell lymphoma. Expression of the Blimp-1 transcription factor, which is critical for promoting B cell differentiation into plasma cells, is repressed by BCL-6. We have investigated the mechanism for how BCL-6 represses Blimp-1 transcription, and have found that BCL-6 regulates the Blimp-1 promoter through a novel mechanism involving AP-1 elements. Specifically, BCL-6 is a potent repressor of transcriptional activity mediated by AP-1 factors. We found that the zinc-finger region of BCL-6 interacts with c-Jun, JunB, and JunD proteins but does not bind c-Fos or Fra-2 proteins. An estrogen receptor ligand binding domain fusion with the BCL-6 zinc finger domain can act as a estrogen-inducible dominant negative protein and increase AP-1 activity in BCL-6+ cells but not in BCL-6- cells, indicating that endogenous BCL-6 represses AP-1 activity. Additionally, we have confirmed a specific interaction between c-Jun and the zinc finger domain of BCL-6 in vivo using a mammalian two-hybrid assay. Repression of AP-1 function by BCL-6 may be a key mechanism for how BCL-6 regulates gene expression to control inflammation, lymphocyte differentiation, and lymphomagenesis.

Original languageEnglish
Pages (from-to)1922-1929
Number of pages8
JournalJournal of Immunology
Volume169
Issue number4
StatePublished - Aug 15 2002

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Transcription Factor AP-1
B-Cell Lymphoma
B-Lymphocytes
Zinc Fingers
Cell Differentiation
Repressor Proteins
Two-Hybrid System Techniques
Proteins
Plasma Cells
Estrogen Receptors
Estrogens
Transcription Factors

ASJC Scopus subject areas

  • Immunology

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Repression of AP-1 function : A mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene. / Vasanwala, Farha H.; Kusam, Saritha; Toney, Lisa M.; Dent, Alexander.

In: Journal of Immunology, Vol. 169, No. 4, 15.08.2002, p. 1922-1929.

Research output: Contribution to journalArticle

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