Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases
|Autoři||KOTALA Vladimír — ULDRIJAN S. — HORKÝ Marcel — TRBUŠEK M. — STRNAD M. — VOJTĚŠEK Bořivoj|
|Druh||Článek v odborném periodiku|
|Citace||KOTALA, Vladimír, S. ULDRIJAN, Marcel HORKÝ, M. TRBUŠEK, M. STRNAD a Bořivoj VOJTĚŠEK. Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases. Cellular and Molecular Life Sciences, Bäsel: Birkhaeuser Verlag, 2001, roč. 58, č. 9, s. 1333-1339. ISSN 1420-682X.|
|Obor||Genetika a molekulární biologie|
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.
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