Mad1 is a transcriptional repressor of Bcl-6.
Mol Immunol
; 43(12): 1965-71, 2006 May.
Article
in En
| MEDLINE
| ID: mdl-16423395
ABSTRACT
Bcl-6, a major regulator of B lymphocyte function that contributes to neoplastic transformation of B cells, is expressed in activated germinal center (GC) B cells and down-regulated during terminal differentiation to plasma cells. Regulation of Bcl-6 expression is incompletely characterized. Terminal B cell differentiation is associated with down-regulation of Bcl-6, activation of Blimp-1, modulation of Myc, and specifically with the up-regulation of the Mad1 and Mad4 transcription factors, which play a critical role in cell differentiation and cell cycle regulation. Because the Mad E-box consensus binding site is present in the upstream promoter of Bcl-6, we investigated whether Bcl-6 may be under control of the Mad1 transcription factor. Anti-sense Mad1 oligonucleotides abrogated the down-regulation of Bcl-6 expression that occurred during in vitro differentiation of mouse splenic B cells induced by dextran-conjugated anti-IgD Ab and IL-5. Transduction of the WEHI 231 B cell line with retroviruses expressing Mad1 down-regulated Bcl-6 expression. Expression of the 5' upstream promoter region of Bcl-6 was down-regulated by co-expression of Mad1. Last, chromatin immunoprecipitation assays with anti-Mad1 Ab demonstrated in vivo interaction of Mad1 with the Bcl-6 promoter region. The findings suggest that Mad1 is a transcriptional repressor of Bcl-6.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/
Proto-Oncogene Proteins c-bcl-6
Limits:
Animals
Language:
En
Journal:
Mol Immunol
Year:
2006
Document type:
Article
Affiliation country:
United States