MALIGNANT TRANSFORMATION OF NIH3T3 CELLS BY OVEREXPRESSION OF MOT-2 PROTEIN

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.