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

74 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis'. Together they form a unique fingerprint.

  • Cite this

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