Caspase-resistant golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors

Rebecca S. Maag, Marie Mancini, Antony Rosen, Carolyn E Machamer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3019-3027
Number of pages9
JournalMolecular Biology of the Cell
Volume16
Issue number6
DOIs
StatePublished - 2005

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Death Domain Receptors
Secretory Pathway
Caspases
Ligation
Apoptosis
Endoplasmic Reticulum Stress
Golgi Apparatus
Initiator Caspases
Anisomycin
Brefeldin A
Cell Line
Thapsigargin
Staurosporine
Dithiothreitol
Etoposide
Pharmaceutical Preparations
Signal Transduction
Membranes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Caspase-resistant golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors. / Maag, Rebecca S.; Mancini, Marie; Rosen, Antony; Machamer, Carolyn E.

In: Molecular Biology of the Cell, Vol. 16, No. 6, 2005, p. 3019-3027.

Research output: Contribution to journalArticle

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