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Transcriptional regulation

Modification by nuclear export?

Nature volume 398, pages 200–201 (1999)Cite this article

The length of time that transcription factors remain active in the nucleus is critical for regulating gene transcription. Transcription factors — or enzymes that modulate their activity — are transported into or out of the nucleus by proteins that recognize nuclear-localization signals (NLS) and nuclear-export signals (NES), respectively1,2. There are several ways to regulate the relative accessibility of NES and NLS: by post-translational modification of nearby residues; by changes in protein structure; or by interaction of the NLS or NES with specific regulatory proteins. On page 256of this issue, Zhu and McKeon3 invoke a variation of the third mechanism to explain the regulated nuclear export of NF-AT4, a transcription factor that has both an NLS and an NES.

Since they were identified a few years ago, proteins of the NF-AT family have been attractive models for studying nuclear import and export4,5,6,7,8,9,10. In resting cells, NF-AT proteins reside in the cytoplasm — their NLS is masked, directly or indirectly, by phosphorylation of specific serine residues in the NF-AT regulatory domain11,12. In stimulated cells, an increase in intracellular calcium activates a phosphatase called calcineurin, which dephosphorylates the ‘masking’ residues, exposing the NLS and initiating nuclear import. In this way, the NLS is exposed and the NF-AT proteins enter the nucleus. But if the activity of calcineurin drops, NF-AT proteins are exported from the nucleus and NF-AT-dependent transcription stops5,6,7. Nuclear export is accompanied by rephosphorylation of the NF-AT regulatory domain5,6, and it is an active process3,9,10 mediated by Crm1, an export receptor that recognizes the leucine-rich class of NES1,2.

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Figure 1: Regulation of the nuclear import and export of NF-AT4.

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Authors and Affiliations

  1. the Center for Blood Research and Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Patrick G. Hogan & Anjana Rao

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  1. Patrick G. Hogan
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  2. Anjana Rao
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Hogan, P., Rao, A. Modification by nuclear export?. Nature 398, 200–201 (1999). https://doi.org/10.1038/18327

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