CDC25A phosphatase is a target of E2F and is required for efficient E2F- induced S phase

Elena Vigo, Heiko Müller, Elena Prosperini, Guus Hateboer, Peter Cartwright, Maria Cristina Moroni, Kristian Helin

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

Functional inactivation of the pRB pathway is a very frequent event in human cancer, resulting in deregulated activity of the E2F transcription factors. To understand the functional role of the E2Fs in cell proliferation, we have developed cell lines expressing E2F-1, E2F-2, and E2F-3 fused to the estrogen receptor ligand binding domain (ER). In this study, we demonstrated that activation of all three E2Fs could relieve the mitogen requirement for entry into S phase in Rat1 fibroblasts and that E2F activity leads to a shortening of the G0-G1 phase of the cell cycle by 6 to 7 h. In contrast to the current assumption that E2F-1 is the only E2F capable of inducing apoptosis, we showed that deregulated E2F-2 and E2F-3 activities also result in apoptosis. Using the ERE2F-expressing cell lines, we demonstrated that several genes containing E2F DNA binding sites are efficiently induced by the E2Fs in the absence of protein synthesis. Furthermore, CDC25A is defined as a novel E2F target whose expression can be directly regulated by E2F-1. Data showing that CDC25A is an essential target for E2F-1, since its activity is required for efficient induction of S phase by E2F-1, are provided. Finally, our results show that expression of two E2F target genes, namely CDC25A and cyclin E, is sufficient to induce entry into S phase in quiescent fibroblasts. Taken together, our results provide an important step in defining how E2F activity leads to deregulated proliferation.

Original languageEnglish
Pages (from-to)6379-6395
Number of pages17
JournalMolecular and Cellular Biology
Volume19
Issue number9
Publication statusPublished - Sep 1999

Fingerprint

S Phase
Phosphoric Monoester Hydrolases
Fibroblasts
E2F Transcription Factors
Apoptosis
Cell Line
Cyclin E
Cell Cycle Resting Phase
G1 Phase
Mitogens
Estrogen Receptors
Genes
Cell Cycle
Binding Sites
Cell Proliferation
Ligands
DNA
Neoplasms
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Vigo, E., Müller, H., Prosperini, E., Hateboer, G., Cartwright, P., Moroni, M. C., & Helin, K. (1999). CDC25A phosphatase is a target of E2F and is required for efficient E2F- induced S phase. Molecular and Cellular Biology, 19(9), 6379-6395.

CDC25A phosphatase is a target of E2F and is required for efficient E2F- induced S phase. / Vigo, Elena; Müller, Heiko; Prosperini, Elena; Hateboer, Guus; Cartwright, Peter; Moroni, Maria Cristina; Helin, Kristian.

In: Molecular and Cellular Biology, Vol. 19, No. 9, 09.1999, p. 6379-6395.

Research output: Contribution to journalArticle

Vigo, E, Müller, H, Prosperini, E, Hateboer, G, Cartwright, P, Moroni, MC & Helin, K 1999, 'CDC25A phosphatase is a target of E2F and is required for efficient E2F- induced S phase', Molecular and Cellular Biology, vol. 19, no. 9, pp. 6379-6395.
Vigo E, Müller H, Prosperini E, Hateboer G, Cartwright P, Moroni MC et al. CDC25A phosphatase is a target of E2F and is required for efficient E2F- induced S phase. Molecular and Cellular Biology. 1999 Sep;19(9):6379-6395.
Vigo, Elena ; Müller, Heiko ; Prosperini, Elena ; Hateboer, Guus ; Cartwright, Peter ; Moroni, Maria Cristina ; Helin, Kristian. / CDC25A phosphatase is a target of E2F and is required for efficient E2F- induced S phase. In: Molecular and Cellular Biology. 1999 ; Vol. 19, No. 9. pp. 6379-6395.
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