Factors affecting the interaction of asbestos fibres with mammalian cells: a study using cells in suspension

Brown, R. C., Fraser, Elizabeth, Hoskins, J. A. and Evans, C. E. 1991. Factors affecting the interaction of asbestos fibres with mammalian cells: a study using cells in suspension. Annals of Occupational Hygiene 35 (1) , pp. 25-34. 10.1093/annhyg/35.1.25

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Abstract

Previous studies have shown that nuclear levels of glycogen synthase kinase-3 (GSK-3) are dynamically regulated and may affect access of GSK-3 to its substrates. In this study we show that the GSK-3-binding protein Frat/GBP regulates the nuclear export of GSK-3. We show that Frat/GBP contains a nuclear export sequence that promotes its own nuclear export and that of associated GSK-3. Treating cells with leptomycin B increased nuclear levels of endogenous GSK-3 suggesting that an endogenous process targets GSK-3 for nuclear export. To investigate this further, we used two approaches to disrupt the interaction between GSK-3 and endogenous Frat. First we isolated mutants of GSK-3 that selectively interfered with Frat binding and found that these mutants were poorly exported. Second we expressed a peptide that competes with Frat for GSK-3 binding and found that it caused endogenous GSK-3 to accumulate in the nucleus. Together these data suggest that Frat may be the endogenous factor that targets GSK-3 for nuclear export. The dynamic expression patterns of Frat mRNAs together with the role of Frat in mediating GSK-3 nuclear export have important implications for the control of the substrate access of GSK-3 in several signaling pathways.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology
Publisher:	Oxford University Press
ISSN:	0003-4878
Last Modified:	04 Jun 2017 06:56
URI:	https://orca.cardiff.ac.uk/id/eprint/66352

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