title: Cellular mortality to immortalization: mortalin.
abstract: The roots of cellular mortality-limited capacity of normal cells to divide, and immortalization-unabated proliferation of cancerous cells remain undefined so far. Out of a variety of experimental strategies employed, the cell fusion approach has been proven to be significantly informative. The present article reviews some of the more important recent results and describes the use of natural and conditional aging systems obtained by the fusion of mortal and immortal mouse fibroblasts to identify putative senescence-determining and/or senescence-escaping genes. 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 one, 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 mortality and immortality and also for the early detection of cancerous cells.
authors.affiliation: National Institute of Bioscience and Human-Technology, Agency of Industrial Science and Technology, Ibaraki, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Wadhwa
authors.forename: S C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Y
authors.initials: Y
authors.lastname: Mitsui
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D016922:Cellular Senescence / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D024101:Mitochondrial Proteins; D008954:Models, Biological; D014407:Tumor Cells, Cultured
chemical_list: D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; C080352:mortalin