SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress
| Autor: | Dale Muzzey, Vivian Chen, Daniel N. Itzhak, Enrique M. Garcia-Rivera, Sebastian Schuck, Tamas Szoradi, Georg H. H. Borner, Rolf M Schmidt, Kevin Leiss, Katharina Schaeff, Juan Diaz-Miyar, Peter W. Bircham |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Protein Folding Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligases medicine.medical_treatment N-end rule Saccharomyces cerevisiae Protein degradation Biology Endoplasmic Reticulum Substrate Specificity 03 medical and health sciences Cytosol Stress Physiological Transcription (biology) medicine Molecular Biology Protease Ubiquitin Endoplasmic reticulum Serine Endopeptidases Cell Biology Adaptation Physiological Ubiquitin ligase Cell biology 030104 developmental biology Proteolysis biology.protein Protein folding |
| Zdroj: | Molecular Cell. 70:1025-1037.e5 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2018.04.027 |
| Popis: | Summary When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress. Here, we uncover a regulatory cascade in budding yeast that consists of the hydrophilin protein Roq1/Yjl144w, the HtrA-type protease Ynm3/Nma111, and the ubiquitin ligase Ubr1. Various stresses stimulate ROQ1 transcription. The Roq1 protein is cleaved by Ynm3. Cleaved Roq1 interacts with Ubr1, transforming its substrate specificity. Altered substrate recognition by Ubr1 accelerates proteasomal degradation of misfolded as well as native proteins at the endoplasmic reticulum membrane and in the cytosol. We term this pathway stress-induced homeostatically regulated protein degradation (SHRED) and propose that it promotes physiological adaptation by reprogramming a key component of the quality control machinery. |
| Databáze: | OpenAIRE |
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