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Nature. 1999 Mar 18;398(6724):256-60.

NF-AT activation requires suppression of Crm1-dependent export by calcineurin.

Author information

1
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

Nuclear import of the NF-AT transcription factors during T-cell activation requires the calcium-activated phosphatase calcineurin, which unmasks nuclear-location signals on NF-AT. We show here that the nuclear import of NF-ATs is not sufficient to activate NF-AT target genes, as NF-ATs are subject to a futile cycling across the nuclear envelope owing to engagement with the exportin protein Crm1. Calcineurin suppresses this futile cycling by a non-catalytic mechanism involving the masking of nuclear export signals on NF-AT targeted by Crm1. This clustering of binding sites for calcineurin and Crml on NF-AT establishes an inherent competition between these molecules that imparts exquisite calcium sensitivity to the shuttling dynamics of the NF-AT transcription factors. Such a balance between nuclear import and export may regulate the action of other transcription factors.

PMID:
10094050
DOI:
10.1038/18473
[Indexed for MEDLINE]

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