Identification of a nuclear localization signal, RRMKWKK, in the homeodomain transcription factor PDX-1

Tilo Moede, Barbara Leibiger, Hamedeh Ghanaat Pour, Per Olof Berggren, Ingo B. Leibiger

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Pancreatic duodenal homeobox-containing transcription factor 1 (PDX-1) plays a crucial role in pancreas development and β-cell gene regulation. Absence of PDX-1 leads to pancreas agenesis and its malfunction causes MODY4 diabetes mellitus. PDX-1 has been suggested to be involved in the glucose-dependent regulation of insulin gene transcription. Whereas DNA-binding and transactivation domains of PDX-1 are in the process of being characterized, protein sequences responsible for its nuclear translocation remain unknown. By combining site-directed mutagenesis of putative phosphorylation sites and nuclear localization signal (NLS) motifs with on-line monitoring of GFP-tagged PDX-1 translocation, we demonstrate that the NLS motif RRMKWKK is necessary and in conjunction with the integrity of the 'helix 3' domain of the PDX-1 homeodomain is sufficient for the nuclear import of PDX-1. Furthermore, we show that there is no glucose-dependent cytoplasmic-nuclear cycling of PDX-1. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalFEBS letters
Volume461
Issue number3
DOIs
StatePublished - Nov 19 1999

Keywords

  • Gene expression regulation
  • Nuclear localization signal
  • PDX-1
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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