Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-3-27
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1965-71
pubmed:dateRevised
2008-11-21
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
pubmed:year
2006
pubmed:articleTitle
Mad1 is a transcriptional repressor of Bcl-6.
pubmed:affiliation
Center for Human Genetics and Molecular Pediatric Disease, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural