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

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.

journal_name

Nature

journal_title

Nature

authors

Zhu J,McKeon F

doi

10.1038/18473

keywords:

subject

Has Abstract

pub_date

1999-03-18 00:00:00

pages

256-60

issue

6724

eissn

0028-0836

issn

1476-4687

journal_volume

398

pub_type

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