CDK4-Cyclin D對於細胞生長調控機制之探討

Abstract

Cell growth is the basis of cell self-reproduction driving. The most important standard of cell self-reproduction is to confirm the fidelity. Cell metabolism condition will regrogram during cell growth (metabolic reprogram). The growth factor will stimulate PI3K/AKT/mTOR signaling pathway during cell growth. Production of c-Myc, HIF-1α and Cyclin D will increase after 4E-BP is phosphorylated by mTORC1. Metabolic reprogram is enhanced by c-Myc and it will form a positive feedback loop that stimulate cell growth. However, HIF-1α will antagonize most effect of c-Myc during cell growth and form a negative feedback loop that inhibit cell growth. The prolyl hydroxylase domain (PHD) system will lead to HIF-1α degradation and eliminate the negative feedback loop of HIF-1α during normal cell growth. The studies in Drosophila melanogaster show that overexpression of CDK4-Cyclin D complex can promote cell growth through PHD of Drosophila. It suggests that CDK4-Cyclin D complex may regulate the balance between c-Myc and HIF-1α through the PHD system to promote cell growth. In this study, we treat Fascaplysin to investigate the cell growth regulation mechanism of CDK4-Cyclin D complex. Our results suggest that CDK4-Cyclin D complex may regulate the balance between c-Myc and HIF-1α through the PHD system to promote cell growth in HeLa cell.