Abstract
Lymphocyte enhancer factor-1 (LEF-1) is a member of the LEF-1/TCF family of transcription factors, which have been implicated in Wnt signaling and tumorigenesis. LEF-1 was originally identified in pre-B and T cells, but its function in B lymphocyte development remains unknown. Here we report that LEF-1-deficient mice exhibit defects in pro-B cell proliferation and survival in vitro and in vivo. We further show that Lef1-/- pro-B cells display elevated levels of fas and c-myc transcription, providing a potential mechanism for their increased sensitivity to apoptosis. Finally, we establish a link between Wnt signaling and normal B cell development by demonstrating that Wnt proteins are mitogenic for pro-B cells and that this effect is mediated by LEF-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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B-Lymphocytes / cytology*
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B-Lymphocytes / metabolism
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Division
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Cell Survival
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DNA, Complementary
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Glycogen Synthase Kinase 3
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / metabolism
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Leukocyte Common Antigens / analysis
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Leukopoiesis / physiology*
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Lymphoid Enhancer-Binding Factor 1
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-myc / genetics
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Signal Transduction*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Suppressor Protein p53 / genetics
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Wnt Proteins
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Wnt-5a Protein
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Wnt3 Protein
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bcl-X Protein
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fas Receptor / genetics
Substances
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Bcl2l1 protein, mouse
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DNA, Complementary
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DNA-Binding Proteins
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Lef1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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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-myc
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Transcription Factors
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Tumor Suppressor Protein p53
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WNT10B protein, human
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WNT5A protein, human
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Wnt Proteins
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Wnt-5a Protein
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Wnt10b protein, mouse
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Wnt3 Protein
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bcl-X Protein
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fas Receptor
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Leukocyte Common Antigens
Associated data
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GENBANK/M83649
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GENBANK/X01023