A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway

Maria Mudryj, Scott W. Hiebert, Joseph R. Nevins

Research output: Contribution to journalArticle

169 Scopus citations

Abstract

Adenovirus E1A dependent frans-activation of transcription involves the utilization of cellular promoter specific transcription factors. One such factor termed E2F is important for the transcription of the viral E2 gene and appears to be a rate limiting component targeted during the tams-activation event. Since E2F is of cellular origin and likely to be involved in cellular gene control, we have identified E2F binding sites in cellular genes. Examples include the c-myc, c-myb and N-myc protooncogenes, the DHFR gene and the EGF receptor gene. The transcription of these genes is regulated by cell proliferation signals and each falls into the so-called immediate early class: genes that are activated independent of new protein synthesis. Because of these common properties of regulation, we have addressed the possible role of E2F in growth factor dependent activation of transcription. Expression of a c-myc promoter driven CAT gene, transfected into quiescent 3T3 cells, is stimulated by serum addition whereas an identical gene containing mutations in the E2F binding sites is not responsive. The DNA binding activity of E2F is increased 4-fold upon serum stimulation and the kinetics of activation parallel activation of c-myc transcription. Furthermore, this increase in E2F activity is independent of new protein synthesis indicating that serum stimulation results in an activation of a pre-existing factor. These results thus provide strong evidence linking E2F and proliferation dependent control of transcription. We also believe that the E2F transcription factor is the first example of a regulator of the class of immediate early genes that is slowly activated by stimulation of cell proliferation.

Original languageEnglish (US)
Pages (from-to)2179-2184
Number of pages6
JournalEMBO Journal
Volume9
Issue number7
StatePublished - 1990
Externally publishedYes

Keywords

  • Adenovirus
  • E2F
  • Signal transduction
  • Transcription factors

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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