E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis

J. W. Zhu, S. J. Field, L. Gore, M. Thompson, H. Yang, Y. Fujiwara, Robert Cardiff, M. Greenberg, S. H. Orkin, J. DeGregori

Research output: Contribution to journalArticle

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Abstract

E2F activity is critical for the control of the G1 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.

Original languageEnglish (US)
Pages (from-to)8547-8564
Number of pages18
JournalMolecular and Cellular Biology
Volume21
Issue number24
DOIs
StatePublished - Dec 13 2001
Externally publishedYes

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Carcinogenesis
Cell Proliferation
T-Lymphocytes
S Phase
Antigens
Cell Differentiation
Phase Transition
Hematopoietic Stem Cells
Autoimmunity
B-Lymphocytes
Bone Marrow
Lymphocytes
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Zhu, J. W., Field, S. J., Gore, L., Thompson, M., Yang, H., Fujiwara, Y., ... DeGregori, J. (2001). E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. Molecular and Cellular Biology, 21(24), 8547-8564. https://doi.org/10.1128/MCB.21.24.8547-8564.2001

E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. / Zhu, J. W.; Field, S. J.; Gore, L.; Thompson, M.; Yang, H.; Fujiwara, Y.; Cardiff, Robert; Greenberg, M.; Orkin, S. H.; DeGregori, J.

In: Molecular and Cellular Biology, Vol. 21, No. 24, 13.12.2001, p. 8547-8564.

Research output: Contribution to journalArticle

Zhu, JW, Field, SJ, Gore, L, Thompson, M, Yang, H, Fujiwara, Y, Cardiff, R, Greenberg, M, Orkin, SH & DeGregori, J 2001, 'E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis', Molecular and Cellular Biology, vol. 21, no. 24, pp. 8547-8564. https://doi.org/10.1128/MCB.21.24.8547-8564.2001
Zhu, J. W. ; Field, S. J. ; Gore, L. ; Thompson, M. ; Yang, H. ; Fujiwara, Y. ; Cardiff, Robert ; Greenberg, M. ; Orkin, S. H. ; DeGregori, J. / E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. In: Molecular and Cellular Biology. 2001 ; Vol. 21, No. 24. pp. 8547-8564.
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