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

Citation
V. Kotala et al., Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases, CELL MOL L, 58(9), 2001, pp. 1333-1339
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN journal
1420-682X → ACNP
Volume
58
Issue
9
Year of publication
2001
Pages
1333 - 1339
Database
ISI
SICI code
1420-682X(200108)58:9<1333:PIOWPT>2.0.ZU;2-0
Abstract
Activation of the p53 tumour suppressor protein by distinct forms of stress leads to inhibition of cellular proliferation by inducing cell cycle arres t or apoptosis. The cyclin-dependent kinase inhibitor roscovitine has been shown to induce nuclear accumulation of wild-type p53 in human untransforme d and tumour-derived cells. We analyzed the response of different human tum our cell lines to roscovitine treatment with respect to their p53 status. S triking 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 roscovitine. The transcriptional activity of p53 was substantially higher i n roscovitine-treated cells than in cells irradiated with ultraviolet C or ionizing radiation, even though all these agents induced a similar amount o f p53 accumulation. These results highlight the therapeutic potential of ro scovitine as an anticancer drug, especially in tumours retaining a function al wild-type p53 pathway.