Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry

Marina Lomazzi, M. Cristina Moroni, Michael R. Jensen, Emanuela Frittoli, Kristian Helin

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer. In the absence of other genetic alterations, this deregulation results in lack of differentiation, hyperproliferation and apoptosis. The pRB protein acts as a transcriptional repressor by targeting the E2F transcription factors, whose functions are required for entry into S phase. Increased E2F activity can induce S phase in quiescent cells-this is a central element of most models for the development of cancer. We show that although E2F1 alone is not sufficient to induce S phase in diploid mouse and human fibroblasts, increased E2F1 activity can result in S-phase entry in diploid fibroblasts in which the p53-mediated G1 checkpoint is suppressed. In addition, we show that E2F1 can induce S phase in primary mouse fibroblasts lacking pRB. These results indicate that, in addition to acting as an E2F-dependent transcriptional repressor, pRB is also required for the cells to retain the G1 checkpoint in response to unprogrammed proliferative signals.

Original languageEnglish
Pages (from-to)190-194
Number of pages5
JournalNature Genetics
Volume31
Issue number2
DOIs
Publication statusPublished - Jun 2002

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S Phase
Fibroblasts
Diploidy
E2F Transcription Factors
Retinoblastoma Protein
Neoplasms
Apoptosis
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry. / Lomazzi, Marina; Moroni, M. Cristina; Jensen, Michael R.; Frittoli, Emanuela; Helin, Kristian.

In: Nature Genetics, Vol. 31, No. 2, 06.2002, p. 190-194.

Research output: Contribution to journalArticle

Lomazzi, Marina ; Moroni, M. Cristina ; Jensen, Michael R. ; Frittoli, Emanuela ; Helin, Kristian. / Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry. In: Nature Genetics. 2002 ; Vol. 31, No. 2. pp. 190-194.
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