E2F1 and E2F2 Determine Thresholds for Antigen-Induced T-Cell Proliferation and Suppress Tumorigenesis
Copyright policy )E2F1 and E2F2 Determine Thresholds for Antigen-Induced T-Cell Proliferation and Suppress Tumorigenesis
E2F activity is critical for the control of the G(1) to S phase transition. We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation and differentiation, as well as increased tumorigenesis and decreased lymphocyte tolerance. The loss of E2F1 and E2F2 impedes B-cell differentiation, and hematopoietic progenitor cells in the bone marrow of mice lacking E2F1 and E2F2 exhibit increased cell cycling. Importantly, we show that E2F1 and E2F2 double-knockout T cells exhibit more rapid entry into S phase following antigenic stimulation. Furthermore, T cells lacking E2F1 and E2F2 proliferate much more extensively in response to subthreshold antigenic stimulation. Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the development of tumors, and some mice exhibit signs of autoimmunity.
- Howard Hughes Medical Institute United States
- Harvard University United States
- University of Colorado Anschutz Medical Campus United States
- University of Colorado Cancer Center United States
- University of California, Davis United States
Male, Genotype, Blotting, Western, Age Factors, Cell Cycle Proteins, Cell Differentiation, Flow Cytometry, E2F Transcription Factors, DNA-Binding Proteins, Mice, Bromodeoxyuridine, E2F2 Transcription Factor, Animals, Female, Lymph Nodes, Lymphocytes, Antigens, Cell Division, Cells, Cultured, E2F1 Transcription Factor
Male, Genotype, Blotting, Western, Age Factors, Cell Cycle Proteins, Cell Differentiation, Flow Cytometry, E2F Transcription Factors, DNA-Binding Proteins, Mice, Bromodeoxyuridine, E2F2 Transcription Factor, Animals, Female, Lymph Nodes, Lymphocytes, Antigens, Cell Division, Cells, Cultured, E2F1 Transcription Factor
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