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Identification of intracellular partners for the secreted serpin protein c inhibitor /pci/


Protein C inhibitor (PCI) belongs to the family of serpins (serine protease inhibitors). As the name indicates many serpins serve as protease inhibitors but many of them have other non-inhibitory functions. In human PCI is localized in plasma and other body fluids and secretions, in liver, male/female reproductive tract organs, megakaryocytes. and keratinocytes. Human PCI (hPCI) was shown to inhibit a variety of proteases, however its precise biological role is not known at present and the role could differ according to the cell specificity. Recently it was shown by the host group that PCI binds retinoic acid in a time- and dose-dependent way and that in megakaryocytes and other bone marrow cells PCI is predominantly present in nuclei. Furthermore, recent data also suggest that cells morphologically apoptotic contain more PCI antigen. Based on these observations aims of the project are as follows:
1 ) to characterize intracellular reaction partners of PCI
2) to elucidate mechanism(s) involved in the uptake and the nuclear translocation of PCI in leukocytes/HL60 leukemia cells and possibly other cell types
3) to characterize conditions of the uptake and the form of PCI which is preferentially internalized.


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