Wnt Signaling Regulates B Lymphocyte Proliferation through a LEF-1 Dependent Mechanism
Open accessAbstract
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.
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Genetic disruption of LEF1 causes severe reduction of the B220+ cell lineage in mice.
“the genetic disruption of a TCF homolog, lymphoid enhancer factor 1 (LEF1), caused severe reduction of the B220+ cell lineage in mice,29)”
From Mammalian Nemo-like kinase enhances .BETA.-catenin-TCF transcription activity in human osteosarcoma and neuroblastoma cells (2007) · cites this paper as [29]
NLK and LEF1 act collaboratively in the same signaling pathway concerning B-cell proliferation.
“suggesting that both NLK and LEF1 act collaboratively in the same signaling pathway concerning B-cell proliferation.”
From Mammalian Nemo-like kinase enhances .BETA.-catenin-TCF transcription activity in human osteosarcoma and neuroblastoma cells (2007) · cites this paper as [29]
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- Authors
- Reya, T., O'Riordan, M., Okamura, R., Devaney, E., Willert, K., Nusse, R., & Grosschedl, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Grosschedl, Rudolf
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 13
- Issue
- 1
- Pages
- 15-24
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2150902176
- Cited by
- 450
- References
- 0
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 7 · 2023: 13 · 2022: 8 · 2021: 17 · 2020: 17 · 2019: 18 · 2018: 14 · 2017: 12 · 2016: 16 · 2015: 24 · 2014: 17 · 2013: 16 · 2012: 18
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt signaling, LEF1, B cell development, pro-B cells, B cell proliferation, apoptosis, Fas, c-Myc, transcription factors, mitogenic signaling
- MeSH terms
- Wnt-5a Protein, Animals, B-Lymphocytes, Base Sequence, Cell Division, Cell Survival, DNA-Binding Proteins, Gene Expression Regulation, Hematopoietic Stem Cells, Molecular Sequence Data, Proteins, Proto-Oncogene Proteins, Transcription Factors, Signal Transduction, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-myc, Apoptosis, Leukocyte Common Antigens, Calcium-Calmodulin-Dependent Protein Kinases, DNA, Complementary, Mice, Knockout, fas Receptor, Proto-Oncogene Proteins c-bcl-2, Leukopoiesis, Glycogen Synthase Kinase 3, bcl-X Protein, Wnt Proteins, Mice, Lymphoid Enhancer-Binding Factor 1, Wnt3 Protein
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