The growth suppressing gas1 product is a GPI-linked protein

Growth arrest specific (gas) 1 gene product is expressed in non-transformed fibroblasts in response to stimuli driving cells into Go phase. Gas1 has b een demonstrated to inhibit cell proliferation when over-expressed in proli ferating fibroblasts, This activity depends on a function of the p53 protei n independent of its transactivating ability. To better define the pathway leading from Gas1, which is located on the plasma membrane, to p53, we have undertaken a detailed characterization of its topology, We demonstrate tha t the protein undergoes cotranslational modifications in the endoplasmic re ticulum, consisting of signal peptide cleavage, N-linked glycosylation and glycosyl-phosphatidylinositol anchor addition, Immunoelectron microscopy sh ows that, in its mature form, Gas1 is randomly distributed over the outer l eaflet of the plasma membrane and that upon antibody-induced clustering it relocalizes to caveolae, (C) 2000 Federation of European Biochemical Societ ies. Published by Elsevier Science B.V. All rights reserved.