Abstract
The multifunctional transcription factor TFII-I physically and functionally interacts with Bruton's tyrosine kinase in murine B cells. However, the downstream functions of TFII-I in B cells are unknown. Toward achieving this goal, we established stable posttranscriptional silencing of TFII-I in WEHI-231 immature murine B cells, which undergoes growth arrest and apoptosis either upon anti-IgM or TGF-beta signaling. In this study, we show that TFII-I promotes growth arrest of cells in a signal-dependent manner. Unlike control cells, B cells exhibiting loss of TFII-I function fail to undergo arrest upon signaling due to up-regulation of c-Myc expression and concomitant down-regulation of both p21 and p27. Loss of TFII-I is also associated with simultaneous increase in nuclear c-rel and decrease in p50 homodimer binding. Thus, besides controlling c-myc transcription, TFII-I controls B cell proliferation by regulating both nuclear translocation of c-rel and DNA-binding activity of p50 NF-kappaB.
MeSH terms
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Active Transport, Cell Nucleus / genetics
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Active Transport, Cell Nucleus / immunology
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Line
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Cell Nucleus / genetics
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Cell Nucleus / immunology
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Cell Nucleus / metabolism
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Cell Proliferation*
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Down-Regulation / genetics
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Down-Regulation / immunology
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Immunoglobulin M / immunology
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Mice
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NF-kappa B p50 Subunit / genetics
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NF-kappa B p50 Subunit / immunology*
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NF-kappa B p50 Subunit / metabolism
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Proto-Oncogene Proteins c-rel / genetics
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Proto-Oncogene Proteins c-rel / immunology*
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Proto-Oncogene Proteins c-rel / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Transcription Factors, TFII / genetics
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Transcription Factors, TFII / immunology*
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Transcription Factors, TFII / metabolism
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Transforming Growth Factor beta / immunology
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Immunoglobulin M
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NF-kappa B p50 Subunit
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Proto-Oncogene Proteins c-rel
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Transcription Factors, TFII
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Transforming Growth Factor beta