The growth suppressing gas1 product is a GPI-linked protein

• Published in: FEBS letters Vol. 481; no. 2; pp. 152 - 158
• Main Authors: Stebel, Marco, Vatta, Paolo, Ruaro, Maria Elisabetta, Del Sal, Giannino, Parton, Robert G., Schneider, Claudio
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.09.2000
• Subjects: 3T3 Cells; Animals; Cell Cycle Proteins; Cell Division; Cell Membrane - metabolism; Consensus Sequence - physiology; COS Cells; Endoplasmic Reticulum - metabolism; gas1 product; Glutaral; Glycosylphosphatidylinositols - metabolism; GPI-anchored protein; GPI-Linked Proteins; Growth inhibition; Humans; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - ultrastructure; Membrane Proteins; Mice; Microscopy, Immunoelectron; p53 protein; Palmitic Acid - metabolism; Phosphatidylinositol Diacylglycerol-Lyase; Precipitin Tests; Protein Binding; Protein Sorting Signals - physiology; Saccharomyces cerevisiae Proteins; Signal peptide; Tissue Fixation; Transfection; Type C Phospholipases - metabolism; Signal peptide; GPI-anchored protein; gas1 product; Growth inhibition; p53 protein
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)02004-4

Growth arrest specific ( gas) 1 gene product is expressed in non-transformed fibroblasts in response to stimuli driving cells into Go phase. Gas1 has been demonstrated to inhibit cell proliferation when over-expressed in proliferating fibroblasts. This activity depends on a function of the p53 protein 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 that the protein undergoes cotranslational modifications in the endoplasmic reticulum, consisting of signal peptide cleavage, N-linked glycosylation and glycosyl-phosphatidylinositol anchor addition. Immunoelectron microscopy shows that, in its mature form, Gas1 is randomly distributed over the outer leaflet of the plasma membrane and that upon antibody-induced clustering it relocalizes to caveolae.