Cutting Edge: TFII-I controls B cell proliferation via regulating NF-kappaB.
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.
Ashworth
Todd
T
Program in Immmunology, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
Roy
Ananda L
AL
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D019473:Transcription Factors, TFII / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D007075:Immunoglobulin M; D052002:NF-kappa B p50 Subunit; D020569:Proto-Oncogene Proteins c-rel; D019473:Transcription Factors, TFII; D016212:Transforming Growth Factor beta