adapt78 protects cells against stress damage and suppresses cell growth

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.