Abstract
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 alpha (TCR alpha) 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 alpha chain from the ER, as well as a truncated, mutant version of TCR alpha 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Line
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Cytomegalovirus / genetics
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Cytomegalovirus / immunology
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Cytomegalovirus / metabolism
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Cytosol / immunology
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Cytosol / metabolism*
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Cytosol / virology
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Diamide / pharmacology
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Endoplasmic Reticulum / immunology
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Endoplasmic Reticulum / metabolism*
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Endoplasmic Reticulum / virology
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Ethylmaleimide / pharmacology
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Glycosylation
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Histocompatibility Antigens Class I / chemistry
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Oxidation-Reduction
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Protein Folding
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Sequence Deletion
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Viral Proteins / genetics
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Viral Proteins / metabolism
Substances
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Histocompatibility Antigens Class I
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Membrane Proteins
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RNA-Binding Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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US11 protein, herpesvirus
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Viral Proteins
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Diamide
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Ethylmaleimide