Visualization of the ER-to-cytosol dislocation reaction of a type I membrane protein

Edda Fiebiger, Craig Story, Hidde L. Ploegh, Domenico Tortorella

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71 Scopus citations


The human cytomegalovirus gene products US2 and US11 induce proteasomal degradation of MHC class I heavy chains. We have generated an enhanced green fluorescent protein-class I heavy chain (EGFP-HC) chimeric molecule to study its dislocation and degradation in US2- and US11-expressing cells. The EGFP-HC fusion is stable in control cells, but is degraded rapidly in US2- or US11-expressing cells. Proteasome inhibitors induce in a time-dependent manner the accumulation of EGFP-HC molecules in US2- and US11-expressing cells, as assessed biochemically and by cytofluorimetry of intact cells. Pulse-chase analysis and subcellular fractionation show that EGFP-HC proteins are dislocated from the endoplasmic reticulum and can be recovered as deglycosylated fluorescent intermediates in the cytosol. These results raise the possibility that dislocation of glycoproteins from the ER may not require their full unfolding.

Original languageEnglish
Pages (from-to)1041-1053
Number of pages13
JournalEMBO Journal
Issue number5
StatePublished - 1 Mar 2002
Externally publishedYes


  • Dislocation
  • Endoplasmic reticulum
  • HCMV US11
  • HCMV US2
  • Proteasomal degradation


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