Informace o publikaci

Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases

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KOTALA Vladimír ULDRIJAN S. HORKÝ Marcel TRBUŠEK M. STRNAD M. VOJTĚŠEK Bořivoj

Rok publikování 2001
Druh Článek v odborném periodiku
Časopis / Zdroj Cellular and Molecular Life Sciences
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Obor Genetika a molekulární biologie
Popis 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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