CELLULAR MORTALITY TO IMMORTALIZATION - MORTALIN

The roots of cellular mortality-limited capacity of normal cells to di vide, and immortalization-unabated proliferation of cancerous cells re main undefined so far. Out of a variety of experimental strategies emp loyed, the cell fusion approach has been proven to be significantly in formative. The present article reviews some of the more important rece nt results and describes the use of natural and conditional aging syst ems obtained by the fusion of mortal and immortal mouse fibroblasts to identify putative senescence-determining and/or senescence-escaping g enes. The strategy has led to the isolation of a novel 66-kDa protein, mortalin- a unique member of the mouse heat shock protein 70 (hsp 70) family. The intracellular distributions of mortalin, i.e., cytosolic and perinuclear, distinguish the mortal phenotype from the immortal on e, respectively. Consistently, the cytosolic mortalin is seen to have a senescence-inducing function in contrast to the perinuclear mortalin which has no detectable effect on cellular phenotype. It is suggested that mortalin can be exploited to unravel some aspects of cellular mo rtality and immortality and also for the early detection of cancerous cells.