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

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

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  • 1Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
21419860
[PubMed - indexed for MEDLINE]
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