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FEBS Lett. 1999 Nov 19;461(3):229-34.

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

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Karolinska Institutet, Rolf Luft Center of Diabetes Research L6B:01, Department of Molecular Medicine, 171 76, Stockholm, Sweden.


Pancreatic duodenal homeobox-containing transcription factor 1 (PDX-1) plays a crucial role in pancreas development and beta-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.

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