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- Title
F9 embryonal carcinoma cells fail to stop at G1/S boundary of the cell cycle after γ-irradiation due to p21<sup>WAF1/CIP1</sup> degradation.
- Authors
Malashicheva, Anna B; Kislyakova, Tatiana V; Aksenov, Nikolay D; Osipov, Konstantin A; Pospelov, Valery A
- Abstract
We studied the ability of F9 teratocarcinoma cells to arrest in G1/S and G2/M checkpoints after γ-irradiation. Wild-type p53 protein was rapidly accumulated in F9 cells after γ-irradiation, however, this was followed not by a G1/S arrest but by a short and reversible delay of the cell cycle in G2/M. In order to elucidate the reasons of the lack of G1/S arrest in F9 cells, we investigated the expression of p53 downstream target Cdk inhibitor p21WAF1/CIP1. In spite of p53-dependent activation of p21WAF1/CIP1 gene promoter and p21WAF1/CIP1 mRNA accumulation upon irradiation, the p21WAF1/CIP1 protein was not detected by either immunoblot or immunofluorescence techniques. However, the cells treated with a specific proteasome inhibitor lactacystin revealed the p21WAF1/CIP1 protein both in non-irradiated and irradiated cells. Therefore we suggest thatp21WAF1/CIP1 protein is degraded by a proteasome-dependent mechanism in F9 cells and the lack of G1/S arrest after γ-irradiation is due to this degradation. We also examined the expression and activity of cell cycle regulatory proteins: G1- and G2-cyclins and cyclin-dependent kinases. In the absence of functionalp21WAF1/CIP1 inhibitor, the activity of G1 cyclin/Cdk complexes was insufficiently inhibited to cause a G1 arrest, whereas a decrease of cdc2 and cyclin B1-associated kinase activities was enough to contribute to a reversible G2 arrest following γ-irradiation. Afterγ-irradiation, the majority of F9 cells undergo apoptosis implying that wt-p53 likely triggers pro-apoptotic gene expression in DNA damaged cells. Elimination of defected cells might ensure maintenance of genome integrity in the remaining cell population. Oncogene (2000) 19, 3858–3865
- Publication
Oncogene, 2000, Vol 19, Issue 34, p3858
- ISSN
0950-9232
- Publication type
Academic Journal
- DOI
10.1038/sj.onc.1203736