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PMID: 11101517 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum.

The EMBO journal ·Vol. 19 ·No. 23 ·2000-12-01 ·Pages 6440-52

Tyson JR, Stirling CJ

Abstract

Lhs1p is an Hsp70-related chaperone localized in the endoplasmic reticulum (ER) lumen. Deltalhs1 mutant cells are viable but are constitutively induced for the unfolded protein response (UPR). Here, we demonstrate a severe growth defect in Deltaire1Deltalhs1 double mutant cells in which the UPR can no longer be induced. In addition, we have identified a UPR- regulated gene, SIL1, whose overexpression is sufficient to suppress the Deltaire1Deltalhs1 growth defect. SIL1 encodes an ER-localized protein that interacts directly with the ATPase domain of Kar2p (BiP), suggesting some role in modulating the activity of this vital chaperone. SIL1 is a non-essential gene but the Deltalhs1Deltasil1 double mutation is lethal and correlates with a complete block of protein translocation into the ER. We conclude that the IRE1-dependent induction of SIL1 is a vital adaptation in Deltalhs1 cells, and that the activities associated with the Lhs1 and Sil1 proteins constitute an essential function required for protein translocation into the ER. The Sil1 protein appears widespread amongst eukaryotes, with homologues in Yarrowia lipolytica (Sls1p), Drosophila and mammals.

MeSH Terms
Adenosine Triphosphatases/metabolism Amino Acid Sequence Animals Anti-Bacterial Agents/pharmacology Bacterial Proteins/genetics,physiology Carrier Proteins/physiology Cell Division Drosophila/chemistry Electrophoresis, Polyacrylamide Gel Endoplasmic Reticulum/metabolism Genes, Reporter Glutathione/metabolism Glutathione Transferase/metabolism Guanine Nucleotide Exchange Factors HSP70 Heat-Shock Proteins/genetics,metabolism,physiology Humans Immunoblotting Membrane Transport Proteins Molecular Chaperones Molecular Sequence Data Mutation Plasmids/metabolism Precipitin Tests Protein Folding Protein Structure, Tertiary Protein Transport Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae Proteins Sepharose/metabolism Sequence Homology, Amino Acid Suppression, Genetic Time Factors Tunicamycin/pharmacology beta-Galactosidase/metabolism
Chemicals
Anti-Bacterial Agents Bacterial Proteins Carrier Proteins Guanine Nucleotide Exchange Factors HSP70 Heat-Shock Proteins LHS1 protein, S cerevisiae Membrane Transport Proteins Molecular Chaperones Recombinant Fusion Proteins SIL1 protein, S cerevisiae SIL1 protein, human Saccharomyces cerevisiae Proteins Tunicamycin Sepharose Glutathione Transferase beta-Galactosidase Adenosine Triphosphatases Glutathione
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tyson J R
School of Biological Sciences, 2.205 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Stirling C J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.23.6440
Published
2000-12-01
Pages
6440-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305876
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.23.6440 PMC Full Text View journal details
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