Effect And Modification Of MTOR/MAPK Signal Transduction Pathway In Polyploid Cells

Background and objective: polyploidy is the state of having greater than the diploid content of DNA. Polyploidy is very important phenomenon of cell biology and have significant effects during species formation. Meanwhile, Polyploidy determine quantity and function of some critical organs and certain pathology process. In particular, There have close relation between Polyploidy and tumorigenesis. However, the mechanism of polyploidization and regulation is not clear. Megakaryocytes are unique, distinct and obligative polyploid cells,because they all become polyploid cells during development process. Megakaryocytes during the endomitosis enter mitosis and progress through mormal prophase, prometaphase, metaphase, and up to anaphase A,but not to anaphase B,telephase,or cytokinesis. There have two checkpoints , G1/S and G2/M which controls cell cycle progression. So CDKs, cyclins, CKIs of G1/S and G2/M are important in Megakaryocytic polyploidization. Mammal target of rapamycin(mTOR) is a S/T kinase,which regulates cell growth (cell mass and cell size) and cell cycle progression through G1/S transition. Some Investigations have indicated that 4EBP1/eIF4E and P70S6K1 are essential for mTOR pathway dependent G1 process. mTOR also participate in regulation of Megakaryocytopoiesis. Phosphorylation of p70S6K1 and 4E-BP1 was diminished in thrombopoietin- cultured human MKs after rapamycin treatment. Rapamycin induced an inhibition in the G1/S transition and a decrease in the mean MK ploidy via a diminution of p21 and cyclin D3 occurring at a transcriptional level. mitogen activated protein kinase(MAPK) is a series of kinases in intracellular several signal transduction. P70S6K1, MNK1 and 4EBP1 participate in protein...