抄録
Limited replicative potential of cells in culture is a well documented phenomenon in wide variety of systems though the mechanistic routes of this remains to be known. Escape from such divisional restrictions to attain immortalization, unlimited proliferation potential, is a prerequisite for cellular transformation and tumerogenesis. It has been established that cellular mortality is dominant over immortalization and the latter results as the recessive dysfunctions in a limited number of genes/ group of genes or pathways. We have exploited the mouse fibroblast system to trace genes involved in cellular mortality and immortalization. Initially, mortal and spontaneously immortalized fibroblasts were fused and the resulting hybrids were analyzed with respect to their population doublings and protein profiles of fractionated cells. The former confirmed the dominant nature of mortal phenotype over the immortal one and the latter resulted into the identification of a 66-kDa protein associated with mortal phenotype both in its natural (normal mortal fibroblasts) as well as conditional (hybrid mortal fibroblasts) state. Further studies delineated the following aspects: (i) 66-kDa protein is a new member of mouse hsp70 family (ii) it resides in different locales in mortal and immortal cells due to the minor changes in the secondary structure of the protein (iii) microinjection of antibody to senescent mouse fibroblasts induced their transient division (iv) transfection of cDNA clone, isolated from normal fibroblasts and encoding for cytosolic form, induced cellular senescence in N I H 3T3 cells. This 66-kDa protein is named mortalin for its cellular senescence inducing function.
