期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 21, 期 24, 页码 8547-8564出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.21.24.8547-8564.2001
关键词
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资金
- NCI NIH HHS [R01 CA077314-03, R01 CA077314, R01 CA077314-02, P30 CA046934, R01 CA 77314-01, R01 CA 43855, 2P30 CA 46934-09] Funding Source: Medline
- NICHD NIH HHS [P30 HD018655, P30-HD 18655] Funding Source: Medline
- PHS HHS [P30 DR 57516] Funding Source: Medline
E2F activity is critical for the control of the G, 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 mar-row 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.
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