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The human signal peptidase complex acts as a quality control enzyme for membrane proteins

Cells need to detect and degrade faulty membrane proteins to maintain homeostasis. In this study, we identify a previously unknown function of the human signal peptidase complex (SPC)—the enzyme that removes endoplasmic reticulum (ER) signal peptides—as a membrane protein quality control factor. We...

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Main Authors: Zanotti, Andrea (Author) , Coelho, João P. L. (Author) , Kaylani, Dinah (Author) , Singh, Gurdeep (Author) , Tauber, Marina (Author) , Hitzenberger, Manuel (Author) , Avci, Dönem (Author) , Zacharias, Martin (Author) , Russell, Robert B. (Author) , Lemberg, Marius (Author) , Feige, Matthias J. (Author)
Format: Article (Journal)
Language:English
Published: 1 Dec 2022
In: Science
Year: 2022, Volume: 378, Issue: 6623, Pages: 996-1000
ISSN:1095-9203
DOI:10.1126/science.abo5672
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/science.abo5672
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/science.abo5672
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Author Notes:Andrea Zanotti, João P. L. Coelho, Dinah Kaylani, Gurdeep Singh, Marina Tauber, Manuel Hitzenberger, Dönem Avci, Martin Zacharias, Robert B. Russell, Marius K. Lemberg and Matthias J. Feige
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Summary:Cells need to detect and degrade faulty membrane proteins to maintain homeostasis. In this study, we identify a previously unknown function of the human signal peptidase complex (SPC)—the enzyme that removes endoplasmic reticulum (ER) signal peptides—as a membrane protein quality control factor. We show that the SPC cleaves membrane proteins that fail to correctly fold or assemble into their native complexes at otherwise hidden cleavage sites, which our study reveals to be abundant in the human membrane proteome. This posttranslocational cleavage synergizes with ER-associated degradation to sustain membrane protein homeostasis and contributes to cellular fitness. Cryptic SPC cleavage sites thus serve as predetermined breaking points that, when exposed, help to target misfolded or surplus proteins for degradation, thereby maintaining a healthy membrane proteome.
Item Description:Gesehen am 27.02.2023
Physical Description:Online Resource
ISSN:1095-9203
DOI:10.1126/science.abo5672

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