title: Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded protein response pathway.
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.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: R
authors.initials: R
authors.lastname: Casagrande
authors.forename: P
authors.initials: P
authors.lastname: Stern
authors.forename: M
authors.initials: M
authors.lastname: Diehn
authors.forename: C
authors.initials: C
authors.lastname: Shamu
authors.forename: M
authors.initials: M
authors.lastname: Osario
authors.forename: M
authors.initials: M
authors.lastname: Zúñiga
authors.forename: P O
authors.initials: PO
authors.lastname: Brown
authors.forename: H
authors.initials: H
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D011489:Protein Denaturation; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction
chemical_list: D005656:Fungal Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D018840:HSP70 Heat-Shock Proteins; C060153:KAR2 protein, yeast; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases