細胞増殖のしくみ―細胞周期，癌遺伝子，細胞老化-j-stage.pdfVIP

YAKUGAKU ZASSHI 126(11) 1087―1115 (2006) 2006 The Pharmaceutical Society of Japan ―Reviews― 細胞増殖のしくみ―細胞周期，癌遺伝子，細胞老化― 井出利憲 Mechanism of Cell Proliferation―Cell Cycle, Oncogenes, and Senescence Toshinori IDE Department of Cellular and Molecular Biology, Division of Integrated Medical Science, Graduated School of Biomedical Sciences, Hiroshima University, 1 2 3 Kasumi, Minami-ku, Hiroshima City 734 8551, Japan ( ) Received August 2, 2006 Cell proliferation is regulated through a transition between the G0 phase and cell cycle. We isolated a mammalian temperature-sensitive mutant cell line defective in the function from the G0 phase to cell cycle. Senescent human somatic cells fail to enter into the cell cycle from the G0 phase with stimulation by any growth factor. Telomere shortening was found to be a cause of cellular senescence, and reexpression of telomerase immortalized human somatic cells. Immortal- ized human somatic cells showed normal phenotypes and were useful not only for basic research but also for clinical and applied ˆelds. The importance of p53 and p21 activation/induction i now well accepted in the signal transduction process from telomere shortening to growth arrest, but the precise mechanism is largely unknown as yet. We found that the MAP kinase cascade and histone acetylase have an important role in the signaling