title: Nuclear import of early growth response-1 involves importin-7 and the novel nuclear localization signal serine-proline-serine.
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.
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Chen
authors.forename: Mary Y
authors.initials: MY
authors.lastname: Liu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Parish
authors.forename: Beng H
authors.initials: BH
authors.lastname: Chong
authors.forename: Levon
authors.initials: L
authors.lastname: Khachigian
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D019913:Nuclear Localization Signals / Q000235:genetics; D011392:Proline / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics
chemical_list: D051766:Early Growth Response Protein 1; C466996:IPO7 protein, human; D028884:Karyopherins; D019913:Nuclear Localization Signals; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D012694:Serine; D011392:Proline