Use of the E2F Transcription Factor by DNA Tumor Virus Regulatory Proteins

  • W. D. Cress
  • J. R. Nevins
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 208)


In most cases the normal host cell for infection by the DNA tumor virus is a quiescent, terminally differentiated cell that is not dividing. Various experiments have demonstrated that upon infection these cells are stimulated to enter S phase, as indicated by the synthesis of cellular DNA and the induction of activities associated with DNA replication, particularly those enzymes involved in deoxynucleotide biosynthesis (Hatanaka and Dulbecco 1966; Ledinko 1968; Yamashita and Shimojo 1969; Dulbecco et al. 1965; Frearson et al. 1965, 1966; Hartwell et al. 1965; Kara and Weil 1967; Kit et al. 1966a, b, 1967a, b; Sheinin 1966). This viral-mediated S phase induction almost certainly reflects the need of these viruses to create an environment appropriate for viral DNA synthesis since the levels of deoxynucleotides are low in quiescent cells and normally rise only when cells are stimulated to enter S phase (Bjorklund et al. 1990; Engstrom et al. 1985). Thus, the normal host for infection by these viruses, a nongrowing cell, is not an environment conducive to DNA replication. The capacity of the DNA tumor viruses to drive a quiescent cell into S phase is dependent largely on the action of the viral regulatory proteins that include adenovirus E1A, SV40 T antigen, and human papillomavirus (HPV) E7. These are also viral proteins that possess oncogenic activity through their common ability to inactivate the retinoblastoma gene product Rb. Indeed, it is now clear that the ability of these viral proteins to promote entry into S phase, so as to create an environment that facilitates viral DNA replication, also results in a loss of cell growth control when a viral infection cannot proceed to completion. Recent developments have led to the realization that these viral proteins mediate these events through the activation of the E2F transcription factor, and studies of their interactions have provided considerable insight into the basic mechanisms of cell growth control and oncogenesis.


Polyoma Virus Cellular Transcription Factor Retinoblastoma Gene Product Adenovirus Early Region Mammalian Ribonucleotide Reductase 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • W. D. Cress
    • 1
  • J. R. Nevins
    • 1
  1. 1.Department of Genetics, Howard Hughes Medical InstituteDuke University Medical CenterDurhamUSA

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