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.