Document Detail

Targeting of nonkaryophilic cell-permeable peptides into the nuclei of intact cells by covalently attached nuclear localization signals.
MedLine Citation:
PMID:  12119035     Owner:  NLM     Status:  MEDLINE    
Dermaseptins are a family of antimicrobial peptides that lyse target bacterial cells by destabilization of their membranes. Here we present a novel application of a peptide derived from the dermaseptin S4, S4(13). At nontoxic concentrations, fluorescently labeled S4(13) was able to penetrate intact cultured HeLa cells but essentially failed to enter their nuclei despite its low molecular weight. Covalent attachment of nuclear localization signal (NLS) motifs of the SV40-T-antigen and of the HIV-1 Rev protein (ARM) conferred karyophilic properties upon the S4(13). The resulting peptides, which were designated as PV-S4(13) and RR-S4(13) penetrated into intact HeLa cells and were able to accumulate within the cells' nuclei. In studies with digitonin-permeabilized cells, nuclear uptake of the PV-S4(13) and the RR-S4(13) peptides showed the same features that characterize active nuclear import. Nuclear import was observed at 37 degrees C, was ATP-dependent, and was inhibited by the free peptides bearing the SV40 NLS and the Rev and Tat ARMs. Microinjected S4(13) remained in the cytoplasm while microinjected RR-S4(13) was translocated into the cells' nuclei. The new type of cell-permeable "karyophilic" peptides described here may be of potential application as a lead compound for therapeutic purposes, as a tool to study nucleocytoplasmic shuttling in intact cells, and for the delivery of peptides to the nucleus.
Elana Hariton-Gazal; Rina Feder; Amram Mor; Adolf Graessmann; Ruth Brack-Werner; David Jans; Chaim Gilon; Abraham Loyter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  41     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-16     Completed Date:  2002-08-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9208-14     Citation Subset:  IM    
Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
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MeSH Terms
Amino Acid Sequence
Cell Membrane Permeability*
Cell Nucleus / metabolism*
Hela Cells
Molecular Sequence Data
Nuclear Localization Signals*
Peptides / metabolism*
Reg. No./Substance:
0/Nuclear Localization Signals; 0/Peptides

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