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p53 is involved in the p120E4F-mediated growth arrest

Oncogene volume 19, pages 188–199 (2000)Cite this article

Abstract

Control of cell growth and division by the p53 tumor suppressor protein requires its abilities to transactivate and repress specific target genes and to associate in complex with other proteins. Here we demonstrate that p53 binds to the E1A-regulated transcription factor p120E4F, a transcriptional repressor of the adenovirus E4 promoter. The interaction involves carboxy-terminal half of p120E4F and sequences located at the end of the sequence-specific DNA-binding domain of p53. Ectopic expression of p120E4F leads to a block of cell proliferation in several human and murine cell lines and this effect requires the association with wild-type (wt) p53. Although p120E4F can also bind to mutant p53, the growth suppression induced by overexpression of the protein is severely reduced in a cell line that contains mutant p53. These data suggest that p120E4F may represent an important element within the complex network of p53 checkpoint functions.

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Acknowledgements

We are grateful to Jeno Gyuris and Roger Brent for the yeast two-hybrid reagents, to Arnold Levine for the Balb/c (10) 1 and Val5 cell lines as well as for the p53 mutant plasmids, to Caterina Fognani for the pCMV-ΦAP3 expression vector and anti-ΦAP3 antiserum, to Bert Vogelstein for pG13CAT and to John Jenkins for p53 truncations tr338 and tr355. We are grateful to Moshe Oren, Maureen Murphy, Giovanni Blandino, Lawrence Banks, Christian Kühne, Claudio Santoro and Margherita Zanetti for reading the manuscript. We also thank all the people of the Laboratorio Nazionale C.I.B. for comments and helpful suggestions and in particular Stefania Marzinotto for technical assistance. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and MURST-P.R.I.N. Cofin 98 (40%) to G Del Sal. P Sandy is supported by a fellowship from ICGEB (International Centre for Genetic Engineering and Biotechnology).

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Authors and Affiliations

  1. Laboratorio Nazionale, Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, Trieste, 34012, Italy

    Peter Sandy, Monica Gostissa, Valentina Fogal, Loris De Cecco, Katalin Szalay, Claudio Schneider & Giannino Del Sal

  2. Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Universita degli Studi di Trieste, Via L. Giorgeri 1, Trieste, 34012, Italy

    Giannino Del Sal

  3. Dipartimento di Scienze e Technologie Biomediche, Universita degli Studi di Udine, p.le Kolbe 1,33100 Udine, Italy

    Claudio Schneider

  4. Department of Genetics, Duke University Medical Center, Box 3054, Durham, 27710, North Carolina, NC, USA

    Robert J Rooney

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Sandy, P., Gostissa, M., Fogal, V. et al. p53 is involved in the p120E4F-mediated growth arrest. Oncogene 19, 188–199 (2000). https://doi.org/10.1038/sj.onc.1203250

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