Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases
|Original title:||Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases|
|Authors:||Vladimír Kotala, S. Uldrijan, Marcel Horký, M. Trbušek, M. Strnad, Bořivoj Vojtěšek|
|Field:||Genetics and molecular biology|
|Type:||Article in Periodical|
Activation of the p53 tumour suppressor protein by distinct forms of stress leads to inhibition of cellular proliferation by inducing cell cycle arrest or apoptosis. The cyclin-dependent kinase inhibitor roscovitine has been shown to induce nuclear accumulaciuon of wild-derived cells.We analyzed the response of different human tumour cell lines to roscovitine treatment with respect to their p53 status. Striking induction of wild-type p53 protein and dramatic enhancement of p53-dependent transcription, coinciding with p21 WAF1 induction, was observed in wildtype, but not mutant, p53-bearing tumour cells after treatment with roccovitine. The transcriptional activity of p53 was substantially higher in roscovitine-treated cells than in cells irradiated with ultravioilet C or ionizing radiation, even though all these agents induced a similar amount of p53 accumulation. These results highlight the therapeutic potential of roscovitine as an anticancer drug, especially in tumours retaining a functional wild-type p53 pathway.