Nuclear import of early growth response-1 involves importin-7 and the novel nuclear localization signal serine-proline-serine

Int J Biochem Cell Biol. 2011 Jun;43(6):905-12. doi: 10.1016/j.biocel.2011.03.004. Epub 2011 Mar 17.

Abstract

A three amino acid sequence, Ser/Thr-Pro-Ser/Thr, was recently identified and characterized as a novel nuclear localization signal (Chuderland et al., 2008). The immediate-early gene product, early growth response-1 is a three zinc finger containing transcription factor implicated in a wide variety of pathologies, and has a bipartite nuclear localization domain identified two decades ago. Efficient nuclear localization of Egr-1 is vital to its function as a transcription factor. Interestingly, Egr-1 also contains a C-terminal SPS domain (residues 482-484 in murine Egr-1). We hypothesized that (482)SPS(484) may also serve as a novel nuclear localization signal in Egr-1. We found that this sequence directs Egr-1 to the nucleus in transfected Chinese hamster ovary cells and show by co-immunoprecipitation analysis that Egr-1 forms a complex with importin-7. (482)SPS(484) is required for Egr-1's interaction with importin-7. Moreover, importin-7 knockdown with RNAi showed that Egr-1 nuclear translocation is importin-7-dependent. This study demonstrates that the nuclear translocation of Egr-1 is partially dependent on (482)SPS(484) and involves importin-7, and sheds light on the molecular mechanisms regulating the cellular localization of this pathophysiologically important transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Animals
  • CHO Cells
  • Cell Nucleus / metabolism*
  • Cricetinae
  • Cricetulus
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Nuclear Localization Signals / genetics
  • Proline / genetics
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics
  • RNA, Small Interfering / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Serine / genetics

Substances

  • Early Growth Response Protein 1
  • IPO7 protein, human
  • Karyopherins
  • Nuclear Localization Signals
  • RNA, Small Interfering
  • Receptors, Cytoplasmic and Nuclear
  • Serine
  • Proline