title: The growth suppressing gas1 product is a GPI-linked protein.
abstract: 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.
authors.affiliation: Laboratorio Nazionale Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Padriciano 99, 34012 Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Stebel
authors.forename: P
authors.initials: P
authors.lastname: Vatta
authors.forename: M E
authors.initials: ME
authors.lastname: Ruaro
authors.forename: G
authors.initials: G
authors.lastname: Del Sal
authors.forename: R G
authors.initials: RG
authors.lastname: Parton
authors.forename: C
authors.initials: C
authors.lastname: Schneider
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism*; D016384:Consensus Sequence / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D058851:GPI-Linked Proteins; D005976:Glutaral; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins; D051379:Mice; D016253:Microscopy, Immunoelectron; D019308:Palmitic Acid / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011233:Precipitin Tests; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D016707:Tissue Fixation; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C066709:GAS1 protein, S cerevisiae; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins; D019308:Palmitic Acid; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D005976:Glutaral