The murine mortalin genes, mot-1 and mot-2, are members of the hsp70 f
amily of proteins and differ from each other by only two amino acid re
sidues. Mot-1 is expressed in normal cells and has pancytosolic cellul
ar distribution whereas mot-2 is found in the perinuclear region of im
mortal cells. We report here that a high level of expression of mot-2
protein resulted in malignant transformation of cells as analysed by a
nchorage independent growth and nude mice assays. A high level of prot
ein expression is attributed to the 900 bp 3' untranslated region of t
he cDNA which does not have any transforming activity per se. Mortalin
cDNA clones isolated from human transformed cells were also found to
have transforming activity in similar assays and a high level of expre
ssion was apparent in some of the human immortalized cells that showed
non-pancytosolic mortalin immunofluorescence, Taken together, the dat
a suggest that nonpancytosolic mortalin may have a role in tumorigenes
is.