Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism.
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.
Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, San Francisco, 94143, USA.
T
T
Reya
M
M
O'Riordan
R
R
Okamura
E
E
Devaney
K
K
Willert
R
R
Nusse
R
R
Grosschedl
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D019891:Leukopoiesis / Q000502:physiology*; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000235:genetics
C494812:Bcl2l1 protein, mouse; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C491119:WNT10B protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C102068:Wnt10b protein, mouse; D060508:Wnt3 Protein; D051020:bcl-X Protein; D019014:fas Receptor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D017493:Leukocyte Common Antigens