ISSN:
1573-675X
Keywords:
Apoptosis
;
BAX
;
caffeine
;
cell cycle
;
p53
;
radiation.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract The p53 tumour suppressor is stabilised following exposure to genotoxic agents, such as γ-radiation. Cell responses to p53 stabilisation include induction of apoptosis and/or cell cycle arrest. Several studies have suggested that γ-radiation stabilises p53 by blocking ubiquitin mediated proteolysis. Here we have compared the biological activities of p53 stabilized following exposure to γ-radiation or treatment with the proteosome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) in MCF7 cells with wild type p53. Stabilisation of p53 by ALLN was reversible and was not blocked by caffeine. Although ALLN was a more effective p53 stabilising agent than γ-radiation, ALLN was not as effective at inducing cell cycle arrest/apoptosis as γ-radiation. Although p53 stabilised by ALLN and γ-radiation were both able to bind DNA and activate transcription, ALLN did not increase expression of BAX, which is involved in p53-induced apoptosis. Therefore, p53 stabilised by different agents is not always biologically active to the same extent and additional alterations triggered by γ-radiation may enable p53 to activate a subset of critical target genes, such as BAX, which are required for p53 responses.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1009614726059
