R. Wadhwa et al., INDUCTION OF CELLULAR SENESCENCE BY TRANSFECTION OF CYTOSOLIC MORTALIN CDNA IN NIH-3T3-CELLS, The Journal of biological chemistry, 268(30), 1993, pp. 22239-22242
We have recently identified a novel member of hsp70 family (mortalin)
as a mortality marker (Wadhwa, R., Kaul, S. C., Ikawa, Y., and Sugimot
o, Y. (1993) J. Biol. Chem. 268, 6615-6621). It has distinct intracell
ular distribution in mortal and immortal fibroblasts. Here, we report
that the cytosolic (mot-1) and the perinuclear (mot-2) forms of mortal
in cDNA cloned from mortal and immortal cells, respectively, differ by
only two bases in the open reading frame, resulting in two amino acid
changes. The induced expression of the cytosolic form by transfection
of mot-1 cDNA (isolate from CD1-ICR mouse embryonic fibroblasts) to N
IH 3T3 cells induced cellular senescence. However, the perinuclear for
m expressed by mot-2 cDNA (isolate from NIH 3T3 cells) did not yield a
n equivalent effect. The data suggest the senescence-inductive functio
n of cytosolic mortalin and implicitly point to a genetic event involv
ed in immortalization.