Endoplasmic reticulum stress differentially inhibits endoplasmic reticulum and inner nuclear membrane protein quality control degradation pathways
| Autor: | Brian J. Snow, Laura N. Scanameo, Adrian B. Mehrtash, Bryce W. Buchanan, Avery M. Runnebohm, Mark Hochstrasser, Eric M. Rubenstein, Courtney L. Broshar |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Nuclear Envelope Ubiquitin-Protein Ligases Saccharomyces cerevisiae Endoplasmic Reticulum Biochemistry 03 medical and health sciences Ubiquitin Gene Expression Regulation Fungal Animals Inner membrane Molecular Biology Protein Unfolding Cell Nucleus 030102 biochemistry & molecular biology biology Chemistry Endoplasmic reticulum Membrane Proteins Membrane Transport Proteins Metalloendopeptidases Cell Biology Endoplasmic Reticulum Stress Translocon biology.organism_classification Phosphoric Monoester Hydrolases Cell biology Ubiquitin ligase Protein Transport Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase 030104 developmental biology Protein Synthesis and Degradation Proteolysis biology.protein Unfolded protein response Asi complex Cattle Plasmids |
| Zdroj: | J Biol Chem |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra119.010295 |
| Popis: | Endoplasmic reticulum (ER) stress occurs when the abundance of unfolded proteins in the ER exceeds the capacity of the folding machinery. Despite the expanding cadre of characterized cellular adaptations to ER stress, knowledge of the effects of ER stress on cellular physiology remains incomplete. We investigated the impact of ER stress on ER and inner nuclear membrane protein quality control mechanisms in Saccharomyces cerevisiae. We analyzed the turnover of substrates of four ubiquitin ligases (Doa10, Rkr1/Ltn1, Hrd1, and the Asi complex) and the metalloprotease Ste24 in induced models of ER stress. ER stress did not substantially impact Doa10 or Rkr1 substrates. However, Hrd1-mediated destruction of a protein that aberrantly engages the translocon (Deg1-Sec62) and substrates with luminal degradation signals was markedly impaired by ER stress; by contrast, Hrd1-dependent degradation of proteins with intramembrane degrons was largely unperturbed by ER stress. ER stress impaired the degradation of one of two Asi substrates analyzed and caused a translocon-clogging Ste24 substrate to accumulate in a form consistent with persistent translocon occupation. Degradation of Deg1-Sec62 in the absence of stress and stabilization during ER stress were independent of four ER stress–sensing pathways. Our results indicate ER stress differentially impacts degradation of protein quality control substrates, including those mediated by the same ubiquitin ligase. These observations suggest the existence of additional regulatory mechanisms dictating substrate selection during ER stress. |
| Databáze: | OpenAIRE |
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