The human cytomegalovirus (HCMV) gene products US2 and US11 dislocate major histocompatibility class I heavy chains from the ER and target them for proteasomal degradation in the cytosol. The dislocation reaction is inhibited by agents that affect intracellular redox potential and/or free thiol status, such as diamide and N-ethylmaleimide. Subcellular fractionation experiments indicate that this inhibition occurs at the stage of discharge from the ER into the cytosol. The T cell receptor α (TCR α) chain is also degraded by a similar set of reactions, yet in a manner independent of virally encoded gene products. Diamide and N-ethylmaleimide likewise inhibit the dislocation of the full-length TCR α chain from the ER, as well as a truncated, mutant version of TCR α chain that lacks cysteine residues. Cytosolic destruction of glycosylated, ER-resident type I membrane proteins, therefore, requires maintenance of a proper redox potential for the initial step of removal of the substrate from the ER environment.
Dislocation of Type I Membrane Proteins from the ER to the Cytosol Is Sensitive to Changes in Redox Potential
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Domenico Tortorella, Craig M. Story, Johannes B. Huppa, Emmanuel J.H.J. Wiertz, Thomas R. Jones, Hidde L. Ploegh; Dislocation of Type I Membrane Proteins from the ER to the Cytosol Is Sensitive to Changes in Redox Potential . J Cell Biol 27 July 1998; 142 (2): 365–376. doi: https://doi.org/10.1083/jcb.142.2.365
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