p53-dependent apoptosis or growth arrest induced by different forms of radiation in U2OS cells: p21WAF1/CIP1 repression in UV induced apoptosis.
Following exposure to DNA damaging agents the p53 tumour-suppressor gene induces either a growth arrest (primarily in G1) or apoptosis. The factors governing which response a cell undertakes, however, are unclear. We find that the osteosarcoma cell line, U2OS, (wild-type for p53) is capable of undergoing either p53 dependent apoptosis or cell cycle arrest in response to distinct forms of radiation. Following exposure to UVC, the majority of U2OS cells were apoptotic within 2 days and cells continued to cycle even as viability was being lost. In contrast, after X-ray treatment, U2OS cells exhibited a cell cycle arrest. Western analysis showed that p53 protein was stabilized to a greater extent by UVC than X-ray. Treatment with X-rays induced p21WAF1/CIP1 whereas p21WAF1/CIP1 expression was specifically repressed at the post-transcriptional level after exposure to UVC. Ectopic expression of high levels of p21WAF1/CIP1, which arrested U2OS cells in G1 and G2, initially conferred considerable protection against UVC-induced apoptosis. Ultimately, however, cells underwent apoptosis indicating that a high level of p21WAF1/CIP1 delays but does not block apoptosis. Taken together, these results show that cell cycle arrest and apoptosis can occur in the same cell type in response to different forms of radiation and that the repression of p21WAF1/CIP1 after UVC may contribute to the efficient induction of apoptosis in response to this particular insult.
Allan
L A
LA
Eukaryotic Gene Organisation and Expression Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX.
Fried
M
M
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D011994:Recombinant Proteins; D015533:Transcriptional Activation / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays; D014965:X-Rays
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53