Degradation of proteins from the ER of S-cerevisiae requires an intact unfolded protein response pathway

被引:151
作者
Casagrande, R
Stern, P
Diehn, M
Shamu, C
Osario, M
Zúñiga, M
Brown, PO
Ploegh, H [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[3] Stanford Univ, Sch Med, Dept Biochem, Howard Hughes Med Inst, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Biol, Howard Hughes Med Inst, Stanford, CA 94305 USA
[5] Univ Calif Santa Cruz, Sinsheimer Labs, Dept Biol, Santa Cruz, CA 95060 USA
关键词
D O I
10.1016/S1097-2765(00)80251-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:729 / 735
页数:7
相关论文
共 29 条
[1]   SEC12 ENCODES A GUANINE-NUCLEOTIDE-EXCHANGE FACTOR ESSENTIAL FOR TRANSPORT VESICLE BUDDING FROM THE ER [J].
BARLOWE, C ;
SCHEKMAN, R .
NATURE, 1993, 365 (6444) :347-349
[2]   Degradation of subunits of the Sec61p complex, an integral component of the ER membrane, by the ubiquitin-proteasome pathway [J].
Biederer, T ;
Volkwein, C ;
Sommer, T .
EMBO JOURNAL, 1996, 15 (09) :2069-2076
[3]   Ubiquitin and the control of protein fate in the secretory and endocytic pathways [J].
Bonifacino, JS ;
Weissman, AM .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 :19-57
[4]   The requirement for molecular chaperones during endoplasmic reticulum-associated protein degradation demonstrates that protein export and import are mechanistically distinct [J].
Brodsky, JL ;
Werner, ED ;
Dubas, ME ;
Goeckeler, JL ;
Kruse, KB ;
McCracken, AA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (06) :3453-3460
[5]   Intracellular signaling from the endoplasmic reticulum to the nucleus [J].
Chapman, R ;
Sidrauski, C ;
Walter, P .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 :459-485
[6]   TRANSCRIPTIONAL INDUCTION OF GENES ENCODING ENDOPLASMIC-RETICULUM RESIDENT PROTEINS REQUIRES A TRANSMEMBRANE PROTEIN-KINASE [J].
COX, JS ;
SHAMU, CE ;
WALTER, P .
CELL, 1993, 73 (06) :1197-1206
[7]   A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response [J].
Cox, JS ;
Walter, P .
CELL, 1996, 87 (03) :391-404
[8]   Exploring the metabolic and genetic control of gene expression on a genomic scale [J].
DeRisi, JL ;
Iyer, VR ;
Brown, PO .
SCIENCE, 1997, 278 (5338) :680-686
[9]  
Eisen MB, 1999, METHOD ENZYMOL, V303, P179
[10]   ANALYSIS OF 2 MUTATED VACUOLAR PROTEINS REVEALS A DEGRADATION PATHWAY IN THE ENDOPLASMIC-RETICULUM OR A RELATED COMPARTMENT OF YEAST [J].
FINGER, A ;
KNOP, M ;
WOLF, DH .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 218 (02) :565-574