Human tissue factor pathway inhibitor-2 is internalized by cells and translocated to the nucleus by the importin system

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Abstract

Tissue factor pathway inhibitor-2 (TFPI-2) is a serine proteinase inhibitor that induces caspase-mediated apoptosis when offered to a variety of tumor cells. In order to investigate the mechanism of TFPI-2-induced apoptosis, we initially studied the uptake and trafficking of TFPI-2 by HT-1080 cells. Exogenously offered TFPI-2 was rapidly internalized and distributed in both the cytosolic and nuclear fractions. Nuclear localization of TFPI-2 was also detected in a variety of endothelial cells constitutively expressing TFPI-2. Nuclear localization of TFPI-2 required a NLS sequence located in its Lys/Arg-rich C-terminal tail comprising residues 191-211, as a TFPI-2 construct lacking the C-terminal tail failed to localize to the nucleus. Complexes of TFPI-2 and importin-α were co-immunoprecipitated from cell lysates of HT-1080 cells either offered or overexpressing this protein, providing evidence that TFPI-2 was shuttled to the nucleus by the importin system. Our results provide the initial description of TFPI-2 internalization and translocation to the nucleus in a number of cells.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume482
Issue number1-2
DOIs
StatePublished - Feb 2009

Keywords

  • Extracellular matrix
  • Importins
  • Nuclear localization
  • Serine proteinase inhibitor
  • TFPI-2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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