Post-transcriptional inactivation of p53 in immortalized murine embryo fibroblast cells.

Abstract:

:The steady-state levels of p53 mRNA and protein were barely detectable by Northern and Western blot analysis in spontaneously immortalized (10)3 and (10)7 murine embryo fibroblast (MEF) cells. But when cells were treated with cycloheximide (CHX) or emetine, expression levels were restored to those observed in primary and immortal (10)10 MEF cells. However, levels of p53 mRNA were not changed in primary or (10)10 MEF cells by CHX treatment. De novo p53 mRNA synthetic rates were similar in primary, (10)10, (10)3, and (10)7 MEF cells treated with or without CHX. Treatment with actinomycin D (ActD) showed that p53 mRNA in primary and (10)10 MEF cells had a relatively long half-life of 22 h, compared to less than 2 h for (10)3 and (10)7 MEF cells. Pulse-chase analysis of p53 mRNA turnover using CHX and ActD showed that the rapid destabilization of p53 mRNA in (10)3 and (10)7 MEF cells could be regulated at the transcriptional and translational levels. In addition, the destabilization of p53 mRNA appeared to occur in the nucleus for (10)3 and (10)7 cells, but not for primary and (10)10 MEF cells. Taken together, the present study demonstrates that inactivation of the p53 gene occurs at the post-transcriptional level by rapid destabilization of its mRNA in the nucleus of spontaneously immortalized (10)3 and (10)7 MEF cells.

journal_name

Oncogene

journal_title

Oncogene

authors

Kim H,You S,Farris J,Foster LK,Foster DN

doi

10.1038/sj.onc.1204423

subject

Has Abstract

pub_date

2001-05-31 00:00:00

pages

3306-10

issue

25

eissn

0950-9232

issn

1476-5594

journal_volume

20

pub_type

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