Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
| Autor: | Markus J. Tamás, Beidong Liu, Nathalie Becker, Sansan Hua, Joana Isabel Rodrigues, Antonia Romero, Stefanie Andersson, Therese Jacobson, Vivien Karl, Arghavan Ashouri, Xinxin Hao, Thomas Nyström, Sebastien Rauch |
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| Rok vydání: | 2020 |
| Předmět: |
Translation
Saccharomyces cerevisiae Proteins Arsenites Saccharomyces cerevisiae Protein aggregation Biology Arsenic chemistry.chemical_compound Protein Aggregates Transcription (biology) Protein biosynthesis Arsenite Translation (biology) Cell Biology Cell Biology and Disease biology.organism_classification Yeast Cell biology Protein quality control Proteostasis chemistry Protein folding Transcription Research Article Protein misfolding |
| Zdroj: | Journal of Cell Science article-version (VoR) Version of Record |
| ISSN: | 1477-9137 |
| Popis: | The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper. Summary: Identification of cellular systems that impinge on protein homeostasis during arsenite stress in yeast, showing that transcriptional and translational control is central for mitigating protein aggregation and toxicity. |
| Databáze: | OpenAIRE |
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