title: Role of zinc finger structure in nuclear localization of transcription factor Sp1.
abstract: Transcription factor Sp1 is localized in the nucleus and regulates gene expression. Our previous study demonstrated that the carboxyl terminal region of Sp1 containing 3-zinc finger region as DNA binding domain can also serve as nuclear localization signal (NLS). However, the nuclear transport mechanism of Sp1 has not been well understood. In this study, we performed a gene expression study on mutant Sp1 genes causing a set of amino acid substitutions in zinc finger domains to elucidate nuclear import activity. Nuclear localization of the GFP-fused mutant Sp1 proteins bearing concomitant substitutions in the first and third zinc fingers was highly inhibited. These mutant Sp1 proteins had also lost the binding ability as to the GC box sequence. The results suggest that the overall tertiary structure formed by the three zinc fingers is essential for nuclear localization of Sp1 as well as dispersed basic amino acids within the zinc fingers region.
authors.affiliation: Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan. kitoh@ph.tokushima-u.ac.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ito
authors.forename: Makiko
authors.initials: M
authors.lastname: Azumano
authors.forename: Chisana
authors.initials: C
authors.lastname: Uwatoko
authors.forename: Kohji
authors.initials: K
authors.lastname: Itoh
authors.forename: Jun
authors.initials: J
authors.lastname: Kuwahara
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000634:Aminoquinolines / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019913:Nuclear Localization Signals / Q000235:genetics / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
chemical_list: D000634:Aminoquinolines; D019913:Nuclear Localization Signals; D016329:Sp1 Transcription Factor; D014105:Tosyl Compounds; C061730:N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide; D015032:Zinc