Abstract
To dissect the requirements of membrane protein degradation from the ER, we expressed the mouse major histocompatibility complex class I heavy chain H-2K(b) in yeast. Like other proteins degraded from the ER, unassembled H-2K(b) heavy chains are not transported to the Golgi but are degraded in a proteasome-dependent manner. The overexpression of H-2K(b) heavy chains induces the unfolded protein response (UPR). In yeast mutants unable to mount the UPR, H-2K(b) heavy chains are greatly stabilized. This defect in degradation is suppressed by the expression of the active form of Hac1p, the transcription factor that upregulates UPR-induced genes. These results indicate that induction of the UPR is required for the degradation of protein substrates from the ER.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Endoplasmic Reticulum / metabolism*
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Fungal Proteins / metabolism
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Gene Expression Regulation
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H-2 Antigens / genetics
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H-2 Antigens / metabolism*
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HSP70 Heat-Shock Proteins / metabolism
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Membrane Glycoproteins / metabolism
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Mice
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Molecular Chaperones / biosynthesis*
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Oligonucleotide Array Sequence Analysis
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Protein Denaturation
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Protein Folding*
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Protein Serine-Threonine Kinases*
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
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Signal Transduction
Substances
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Fungal Proteins
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H-2 Antigens
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H-2Kb protein, mouse
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HSP70 Heat-Shock Proteins
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KAR2 protein, yeast
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Membrane Glycoproteins
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Molecular Chaperones
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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IRE1 protein, S cerevisiae
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Protein Serine-Threonine Kinases