A study on the control mechanisms of starvation response and cell differentiation, using the developmental system of Dictyostelium

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This work has been done to elucidate precisely genes and their functions, which are involved in control of cellular growth and differentiation, using the developmental system of Dictyostelium cells. New findings done by this work are as follows. (1) The dial gene that are specifically expressed coupling with differentiation of cells from the growth/differentiation transition point (GDT-point) in the cell cycle was found to shares the promoter region with other gene (impA) ; the impA is specifically expressed during the growth phase, while the dial at the initiation of differentiation. By promoter analyses, the regions that regulate their transcription were precisely specified. (2) Dd-TRAP1, a Dictyostelium homologue of mitochondria-localized HSP90 (TRAP-1) was found to be closely involved in the prestarvation response (PSR) and subsequent differentiation after starvation of cells ; the suppression of Dd-trap 1 expression by the RNAi method greatly inhibits the PSR and therefore the initiation of differentiation f starving cells. (3) Dd-TRAP1 changes its localization depending on the cell densities during the growth phase ; Dd-TRAP1 moves extensively to the cell cortex from mitochondria at low cell densities, while it returns again to mitochondria from the cell cortex at higher cell densities. (4) The return of, Dd-TRAP1 is induced by a novel prestarvation-factor-3 (PSF-3) and required for subsequent differentiation of starving cells. (5) A Dictyostelium homologue (DNG1) of the tumor suppressor (ING1) was found to be closely involved in cell differentiation as well as in growth through histone modification. Incidentally, exhaustive analyses of genes involved in starvation response and initiation of differentiation are now in advance as collaborative works with Drs. Adam Kuspa and Gad Shaulsky of Baylor Medical College.