The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function

M Nevels, S Rubenwolf, T Spruss, H Wolf, T Dobner

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

We have recently shown that the adenovirus type 5 E4orf6 protein interacts with the cellular tumor suppressor protein p53 and blocks p53 transcriptional functions. Here we report that the E4orf6 protein can promote focus formation of primary rodent epithelial cells in cooperation with adenovirus E1A and E1A plus E1B proteins. The E4orf6 protein can also inhibit p53-mediated suppression of E1A plus E1B-19kDa-induced focus formation. Mutant analysis of the E4orf6 protein demonstrates that these activities correlate with the ability of the adenovirus protein to relieve transcriptional repression mediated by the carboxyl-terminal region of p53 in transient transfection assays. We further demonstrate that expression of wild-type E4orf6 correlates with a dramatic reduction of p53 steady-state levels in transformed rat cells. Our data demonstrate that adenovirus type 5 encodes two different proteins, E1B-55kDa and E4orf6, that bind to p53 and contribute to transformation by modulating p53 transcriptional functions.
Original languageEnglish
Pages (from-to)1206-11
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number4
Publication statusPublished - 18 Feb 1997

Keywords

  • Adenovirus E1A Proteins
  • Adenovirus E1B Proteins
  • Adenovirus E4 Proteins
  • Adenovirus Early Proteins
  • Animals
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Genes, Tumor Suppressor
  • Kidney
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic
  • Tumor Suppressor Protein p53

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