Source:http://linkedlifedata.com/resource/pubmed/id/16423395
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2006-3-27
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pubmed:abstractText |
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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/Mad protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-6,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0161-5890
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1965-71
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16423395-Animals,
pubmed-meshheading:16423395-B-Lymphocytes,
pubmed-meshheading:16423395-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:16423395-Binding Sites,
pubmed-meshheading:16423395-Cell Differentiation,
pubmed-meshheading:16423395-Cells, Cultured,
pubmed-meshheading:16423395-Down-Regulation,
pubmed-meshheading:16423395-Leukemia, B-Cell,
pubmed-meshheading:16423395-Mice,
pubmed-meshheading:16423395-Mice, Inbred C57BL,
pubmed-meshheading:16423395-Oligonucleotides, Antisense,
pubmed-meshheading:16423395-Promoter Regions, Genetic,
pubmed-meshheading:16423395-Protein Binding,
pubmed-meshheading:16423395-Proto-Oncogene Proteins c-bcl-6,
pubmed-meshheading:16423395-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:16423395-Repressor Proteins,
pubmed-meshheading:16423395-Spleen
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pubmed:year |
2006
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pubmed:articleTitle |
Mad1 is a transcriptional repressor of Bcl-6.
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pubmed:affiliation |
Center for Human Genetics and Molecular Pediatric Disease, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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