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Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors
Correspondence to Raymond A. Poot: r.poot{at}erasmusmc.nl; or Robbert J. Rottier: r.rottier{at}erasmusmc.nl
SRY and other Sox-type transcription factors are important developmental regulators with various implications in human disease. In this study, we identified Exp4 (exportin 4) as an interaction partner of Sox2 in mouse embryonic stem cells and neural progenitors. We show that, besides its established function in nuclear export, Exp4 acts as a bona fide nuclear import receptor for Sox2 and SRY. Thus, Exp4 is an example of a nuclear transport receptor carrying distinct cargoes into different directions. In contrast to a published study, we observed that the import activity of Imp-
(importin-a) isoforms toward Sox2 is negligible. Instead, we found that Imp9 and the Imp-β/7 heterodimer mediate nuclear import of Sox2 in parallel to Exp4. Import signals for the three pathways overlap and include conserved residues in the Sox2 high-mobility group (HMG) box domain that are also critical for DNA binding. This suggests that nuclear import of Sox proteins is facilitated by several parallel import pathways.
© 2009 Gontan et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
R.A. Poot and R.J. Rottier contributed equally to this paper.
Abbreviations used in this paper: ES, embryonic stem; HMG, high-mobility group; IBB, Imp-β–binding domainof Imp-
; MBP, maltose-binding protein; NPC, nuclear pore complex.
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