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.
Originální jazyk angličtina
Obor Genetika a molekulární biologie
Klíčová slova

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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