p53 protein accumulation in addition to the transactivation activity is required for p53-dependent cell cycle arrest after treatment of cells with camptothecin

Oncogene
V JaksT Maimets

Abstract

In this study we characterize the connections between p53-dependent G1 cell cycle arrest, transcriptional activation of the protein and the increase of its intracellular steady-state concentration. Several cell lines expressing wild-type p53 protein were treated with increasing concentrations of DNA-damaging drug camptothecin. Lower doses of the drug caused transcriptional activation of p53, but no accumulation of the protein was detected. Only after a certain threshold dose of camptothecin does the amount of the protein rapidly increase and reach its plateau levels. The threshold dose was different for different cell lines, but the general non-linear profile was similar. Increase of p53 level was accompanied by additional transcriptional activation of some p53 target genes (i.e. waf1), but not the others (mdm2). We demonstrate here that transcriptional activation of p53 after the treatment of camptothecin is not sufficient to cause p53-dependent G1 cell cycle arrest. The latter is observable only after the increase of steady-state level of p53. Low drug concentrations, although accompanied by transcriptional activation of p53, do not cause either p53 protein accumulation nor cell cycle arrest at G1. We propose a model for p53 ...Continue Reading

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Citations

Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Suman JayadevGwenn A Garden
Jul 11, 2003·Nucleic Acids Research·Jianmin Zhou, Carol Prives
May 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elena TassiAndrea Anichini
Jun 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang QiaoPaul Dent
Feb 3, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Mingjuan LiuBret A Hassel
Mar 6, 2015·British Journal of Cancer·A ZajkowiczM Rusin
Sep 21, 2016·Journal of the American Statistical Association·Lisa M PhamEric D Kolaczyk
Mar 15, 2003·Cancer Gene Therapy·Yan Bin DongKelly M McMasters
May 15, 2001·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·M K Kang, N H Park

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