E-Ras improves the efficiency of reprogramming by the acceleration of cell cycle through JNK–Sp1 pathway

Abstract

Embryonic stem (ES) cells are pluripotent stem cells derived from the inner cell mass (ICM) of a blastocyst at least an early-stage preimplantation embryo. ES cells are distinguished by their ability to divide and self-renewal for extended periods. Because of their properties, ES cells are used to treat Alzheimer's disease, Parkinsons disease, and other degenerative diseases. However, ES cell treatment is not unfettered because ES cells have ethical difficulties of using human embryos and tissue rejection problem in transplantation. To solve these problems, ES cell-like cells, which are named induced pluripotent stem (iPS) cells, are generated by various methods, such as defined factors, non-viral inducers or proteins. Generation of iPS cells using protein extracts is depending on the background of ES cells lines. Proteomic analysis of mES cell lines shows that embryonic Ras (E-Ras) is expressed differently in each mES cells and high level of E-Ras in the extracts allows producing iPS cells. In this study, I examined the function of E-Ras as a controller of the cell cycle. Cyclin D and E, the major G1-S transition control factors are up-regulated by E-Ras – JNK signaling pathway. These results prompted us to propose that E-Ras, which can promote cell proliferation, is able to increase efficiency of somatic reprogramming.