We have previously identified several genes whose RNA products are induced
in HA-1 hamster cells under conditions where a cytoprotective adaptive resp
onse is observed. One of these genes, designated adapt78, was found to have
a human homolog with some homology to glucose-regulated protein 78 (Grp78)
. We subsequently determined that adapt78 and grp78 mRNAs are induced by th
e same stress agents and conclude that adapt78 is a stress-response gene an
d putative new member of the grp stress gene family. Here we extend these s
tudies to assess the effect of overexpressing adapt78 on stress protection
and growth arrest. HA-1 cells stably transfected with adapt78 cDNA were fou
nd to exhibit significantly reduced calcium- and hydrogen peroxide-mediated
cytotoxicity as compared with control transfectants. In addition, adapt78
stable overexpressors exhibited significantly reduced cell growth. Both cyt
oprotection and growth arrest accompanied only modest overexpression of ada
pt78. Flow cytometry revealed that the growth arrest occurred in G(1)-phase
. Immunoflourescent analysis revealed that Adapt78 protein exhibits signifi
cant perinuclear staining suggestive of endoplasmic reticulum localization
in addition to cytoplasmic localization. These data indicate that adapt78 i
s both cytoprotective and growth suppressive and that these effects may be
mediated by Adapt78 protein at the endoplasmic reticulum. (C) 2000 Academic
Press.