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

Onderzoeksoutput: ArticleAcademicpeer review

7 Citaten (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.

Originele taal-2English
Pagina's (van-tot)1142-1154
Aantal pagina's13
Nummer van het tijdschrift8
StatusPublished - 14-feb.-2008

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