CORRELATION BETWEEN COMPLEMENTATION GROUP FOR IMMORTALITY AND THE CELLULAR-DISTRIBUTION OF MORTALIN

The dominance of cellular senescence over the immortal phenotype has b een demonstrated by cell fusion experiments utilizing human and mouse cells. Mortalin, a novel 66-kDa member of the murine hsp70 family of p roteins, has recently been identified as a marker of the mortal phenot ype by virtue of its characteristic cytosolic distribution in mortal c ells. Here we report the mortalin immunostaining observations on 21 hu man cell lines. These cell lines have previously been assigned by soma tic cell hybridization analysis to one (18 lines) or more than one (3 lines) of the four complementation groups (A, B, C, and D) for immorta lization. Four patterns of mortalin immunostaining were observed: gran ular-juxtanuclear cap, granular-gradient from nuclear to cell membrane , granular-juxtanuclear arch, and fibrous-perinuclear. In 17 of 18 cel l lines assigned to a single complementation group, the mortalin stain ing corresponded with the complementation group. In two of the three c ell lines previously assigned to multiple complementation groups, the mortalin staining corresponded to one of the assigned groups. Two cell lines, however, exhibited staining patterns which did not match to th eir assigned complementation groups, The basis of correlation between cellular distribution of mortalin and the complementation group remain s unclear at present. However, the data (i) suggest that the intracell ular distribution of mortalin can be used to distinguish mortal and im mortal cells, confirming the association of mortalin with senescence; (ii) provide supportive evidence for the existence of at least four di fferent pathways of immortalization in human cells; and (iii) indicate that mortalin is involved in processes that result in immortalization . (C) 1995 Academic Press, Inc.