Macrophage Migration Inhibitory Factor (mif), The Regulation Of Apoptosis, The Molecular Mechanisms Of Cell Growth And Cycle

In the first section of the dissertation,we have employed a yeast two-hybrid system to isolate a novel Bim-interacting protein,macrophage migration inhibitory factor(MIF).The interaction between MIF and Bim was confirmed by both in vitro and in vivo protein interaction assays.Moreover,MIF may regulate pro-apoptotic activity of Bim and inhibit the release of cytochrome c from mitochondria to the cytosol during apoptosis.This study provides the novel insights into the MIF's anti-apopotic activity and Bim-mediated mitochondria-dependent apoptosis.In the second section of the dissertation,we demonstrate siRNA-mediated knockdown of MIF results in inhibition of cell proliferation and G0/G1 cell cycle arrest in HEK293 cells.To elucidate the molecular mechanism of cell cycle perturbation following MIF knockdown, we employed microarray to investigate the genome-wide expression profile in MIF-deficient cells and normal cells.The dynamic model of MIF-dependent signaling pathways linked to cell cycle machinery were constructed through analyzing gene expression data in the context of the gene ontology and the known biological pathways. We have established an integrate and dynamic signaling network in the MIF knockdown cell.This study provides novel insights into the pleiotropic activities of endogenous MIF, especially its essential and crucial role in cell proliferation and the cell cycle.