title: Caspase-resistant Golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors.
abstract: Golgin-160 is a coiled-coil protein on the cytoplasmic face of the Golgi complex that is cleaved by caspases during apoptosis. We assessed the sensitivity of cell lines stably expressing wild-type or caspase-resistant golgin-160 to several proapoptotic stimuli. Cells expressing a caspase-resistant mutant of golgin-160 were strikingly resistant to apoptosis induced by ligation of death receptors and by drugs that induce endoplasmic reticulum (ER) stress, including brefeldin-A, dithiothreitol, and thapsigargin. However, both cell lines responded similarly to other proapoptotic stimuli, including staurosporine, anisomycin, and etoposide. The caspase-resistant golgin-160 dominantly prevented cleavage of endogenous golgin-160 after ligation of death receptors or induction of ER stress, which could be explained by a failure of initiator caspase activation. The block in apoptosis in cells expressing caspase-resistant golgin-160 could not be bypassed by expression of potential caspase cleavage fragments of golgin-160, or by drug-induced disassembly of the Golgi complex. Our results suggest that some apoptotic signals (including those initiated by death receptors and ER stress) are sensed and integrated at Golgi membranes and that golgin-160 plays an important role in transduction of these signals.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Maag
authors.forename: Marie
authors.initials: M
authors.lastname: Mancini
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Machamer
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D000077614:Golgi Matrix Proteins; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011233:Precipitin Tests; D019311:Staurosporine / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens; D004791:Enzyme Inhibitors; C108388:GOLGA3 protein, human; D000077614:Golgi Matrix Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; D000841:Anisomycin; D005047:Etoposide; D020169:Caspases; D019311:Staurosporine