Abstract
PU.1(+/-)Spi-B(-/-) mice exhibit reduced numbers of immature and mature B lymphocytes, which exhibit severe defects in response to BCR-mediated stimulation and poor survival. We found that expression of c-rel, a member of the Rel/NF-kappa B family, is dramatically reduced in PU.1(+/-)Spi-B(-/-) splenic B cells. Analysis of the murine c-rel promoter identified three PU.1/Spi-B binding sites critical for c-rel promoter activity. Furthermore, reintroduction of Rel protein restored wild-type B cell numbers to mice reconstituted with PU.1(+/-)Spi-B(-/-) bone marrow. These findings are the first to demonstrate that a member of the Rel/NF-kappa B family is directly regulated by Ets proteins and dissect the molecular basis for the function of two Ets factors, PU.1 and Spi-B, in promoting B lymphocyte survival.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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Binding Sites
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Bone Marrow Cells / immunology
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Bone Marrow Transplantation
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Cell Line
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Cell Survival
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Down-Regulation
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Gene Expression Regulation
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Mice
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Mice, Knockout
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-rel / biosynthesis
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Proto-Oncogene Proteins c-rel / genetics*
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RNA, Messenger / biosynthesis
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Spleen / immunology
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Trans-Activators / genetics
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Trans-Activators / physiology*
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transfection
Substances
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-rel
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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proto-oncogene protein Spi-1
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SPIB protein, human