Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors

J Cell Biol. 2009 Apr 6;185(1):27-34. doi: 10.1083/jcb.200810106.

Abstract

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-alpha (importin-a) isoforms toward Sox2 is negligible. Instead, we found that Imp9 and the Imp-beta/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism*
  • HMG-Box Domains
  • Karyopherins / metabolism
  • Karyopherins / physiology*
  • Mice
  • Protein Sorting Signals
  • SOX Transcription Factors / chemistry
  • SOX Transcription Factors / metabolism*
  • SOXB1 Transcription Factors / analysis
  • SOXB1 Transcription Factors / chemistry
  • SOXB1 Transcription Factors / metabolism
  • Sex-Determining Region Y Protein / metabolism

Substances

  • Karyopherins
  • Protein Sorting Signals
  • SOX Transcription Factors
  • SOXB1 Transcription Factors
  • Sex-Determining Region Y Protein
  • Sox2 protein, mouse
  • Sry protein, mouse
  • Xpo4 protein, mouse