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 language | English (US) |
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Pages (from-to) | 58-65 |
Number of pages | 8 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 482 |
Issue number | 1-2 |
DOIs | |
State | Published - Feb 2009 |
Keywords
- Extracellular matrix
- Importins
- Nuclear localization
- Serine proteinase inhibitor
- TFPI-2
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology