Oncogenic pathways impinging on the G2-restriction point

F Foijer, M Simonis, M van Vliet, L Wessels, R Kerkhoven, P K Sorger, H Te Riele

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)


In the absence of mitogenic stimuli, cells normally arrest in G(1/0), because they fail to pass the G1-restriction point. However, abrogation of the G1-restriction point (by loss of the retinoblastoma gene family) reveals a second-restriction point that arrests cells in G2. Serum-starvation-induced G2 arrest is effectuated through inhibitory interactions of p27(KIP1) and p21(CIP1) with cyclins A and B1 and can be reversed through mitogen re-addition. In this study, we have investigated the pathways that allow cell cycle re-entry from this G2 arrest. We provide evidence that recovery from G2 arrest depends on the rat sarcoma viral oncogene (RAS) and phosphatidylinositol-3 kinase pathways and show that oncogenic hits, such as overexpression of c-MYC or mutational activation of RAS can abrogate the G2-restriction point. Together, our results provide new mechanistic insight into multistep carcinogenesis.

Original languageEnglish
Pages (from-to)1142-1154
Number of pages13
Issue number8
Publication statusPublished - 14-Feb-2008


  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic
  • G2 Phase
  • Gene Expression Profiling
  • Genes, ras
  • Mice
  • Multigene Family
  • Oncogenes
  • Phosphatidylinositol 3-Kinases
  • Signal Transduction
  • ras Proteins

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