Preparation of an artificial cell cycle progressor with a novel mechanism.
Control of cell cycle progression in somatic cells or terminally differentiated cells is a key technology for cell-based therapies such as regenerative therapy. We have prepared an artificial cell cycle progression peptide composed of a human immunodeficiency virus-derived Tat protein transduction domain (PTD) and a p53 genetic suppressor element (GSE123). The peptide significantly promoted hepatocyte growth factor-induced DNA synthesis and the proliferation of primary mouse hepatocytes, which are highly differentiated somatic cells. The addition of a nuclear localization signal (NLS) sequence to the peptide increased the internalization of the peptide to the nuclear fraction. Distribution analysis using a fluoresein isothiocyanate-labeled peptide indicated that the NLS enabled the peptide to escape from the lysosomes to the cytosol. As a result, the NLS-Tat-GSE123 peptide induced potent cell proliferation of primary mouse hepatocytes in vitro. The use of this peptide as an artificial cell growth enhancer, bypassing a specific receptor, is a useful tool for the study of regenerative therapy and cell signaling.
Kanki
Keita
K
Department of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo 202-8585, Japan.
Ishijima
Yuko
Y
Watanabe
Yoshifumi
Y
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D015696:Gene Products, tat / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D017931:DNA Primers; D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D017228:Hepatocyte Growth Factor