Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded protein response pathway.
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.
Casagrande
R
R
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stern
P
P
Diehn
M
M
Shamu
C
C
Osario
M
M
Zúñiga
M
M
Brown
P O
PO
Ploegh
H
H
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
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