Ast T~Schuldiner M, 2016

Pubmed ID 26771486
Title The Protease Ste24 Clears Clogged Translocons.
Authors Tslil Ast, Susan Michaelis, Maya Schuldiner
Abstract Translocation into the endoplasmic reticulum (ER) is the first step in the biogenesis of thousands of eukaryotic endomembrane proteins. Although functional ER translocation has been avidly studied, little is known about the quality control mechanisms that resolve faulty translocational states. One such faulty state is translocon clogging, in which the substrate fails to properly translocate and obstructs the translocon pore. To shed light on the machinery required to resolve clogging, we carried out a systematic screen in Saccharomyces cerevisiae that highlighted a role for the ER metalloprotease Ste24. We could demonstrate that Ste24 approaches the translocon upon clogging, and it interacts with and generates cleavage fragments of the clogged protein. Importantly, these functions are conserved in the human homolog, ZMPSTE24, although disease-associated mutant forms of ZMPSTE24 fail to clear the translocon. These results shed light on a new and critical task of Ste24, which safeguards the essential process of translocation.
Citation Cell 2016; 164:103-114

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Paper Phenotype Condition Reference Collection Tested mutants Data Details
Ast T~Schuldiner M, 2016 growth (colony size) expression of clogging-prone Pdi1-DHFR [standard] hap a 4,338 Quantitative

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