Cellular mortal and immortal phenotypes as defined by the limited and
the infinite capacity of cells to divide are the characteristics of no
rmal and cancerous cells in culture. Numerous strategies that have bee
n employed to understand the mechanism(s) of normal as well as tumor c
ell growth have revealed that these are genetically controlled, howeve
r, the genes and the synchronized regulations remain largely undefined
so far. The present report reviews the identification of mortalin, a
novel member of murine hsp70 family of proteins, as a gene involved in
pathways that determine divisional phenotype of cells in vitro. In th
e present study, the anti-proliferative activity of mortalin is demons
trated also in human skin fibroblasts (TIG-73PD) by microinjection of
anti-mortalin antibody. Furthermore, studies on the mortalin immunoflu
orescence patterns in SV40-immortalized pre-crisis and post-crisis hum
an cells have revealed that the change in the intracellular distributi
on of mortalin is linked to the change in the divisional phenotype of
cells. Thus, the studies to resolve the molecular basis of association
of the cytosolically distributed form of mortalin with cellular morta
l phenotype would be important in understanding of the mechanism(s) th
at determine replicative potential of cells in culture.