Cytoplasmic retention of mutant tsp53 is dependent on an intermediate filament protein (vimentin) scaffold.

Abstract:

:The temperature-sensitive mutant tsp53val135 accumulates in the cytoplasm of cells kept at the non-permissive temperature (39 degrees C), but is rapidly transported into the cell nucleus at the permissive temperature (30 degrees C). tsp53 thus may serve as a model for analysing cellular parameters influencing the subcellular location of p53. Here we provide evidence that retention of tsp53 in the cytoplasm at the non-permissive temperature is due to cytoskeletal anchorage of the p53 protein. Two sublines of C6 rat glioma cells differing in their expression of the intermediate filament protein vimentin (vimentin expressing or vimentin negative cells) were stably transfected with a vector encoding tsp53. Whereas cells of vimentin expressing C6 subclones retained tsp53 in the cytoplasm at the non-permissive temperature, cells of vimentin negative subclones exclusively harbored the tsp53 within their nuclei. Intermediate filament deficient cells that had been reconstituted with a full length vimentin protein again showed a cytoplasmic localization of tsp53, whereas in cells expressing a C-terminally truncated (tail-less) vimentin tsp53 localized to the nucleus. We conclude that cytoplasmic sequestration of tsp53 requires an intact intermediate filament system.

journal_name

Oncogene

journal_title

Oncogene

authors

Klotzsche O,Etzrodt D,Hohenberg H,Bohn W,Deppert W

doi

10.1038/sj.onc.1202155

subject

Has Abstract

pub_date

1998-07-02 00:00:00

pages

3423-34

issue

26

eissn

0950-9232

issn

1476-5594

journal_volume

16

pub_type

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