Reich, Stefan and Nguyen, Chi D. L. and Has, Canan and Steltgens, Sascha and Soni, Himanshu and Coman, Cristina and Freyberg, Moritz and Bichler, Anna and Seifert, Nicole and Conrad, Dominik and Knobbe-Thomsen, Christiane B. and Tews, Bjoern and Toedt, Grischa and Ahrends, Robert and Medenbach, Jan (2020) A multi-omics analysis reveals the unfolded protein response regulon and stress-induced resistance to folate-based antimetabolites. NATURE COMMUNICATIONS, 11 (1): 2936. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Stress response pathways are critical for cellular homeostasis, promoting survival through adaptive changes in gene expression and metabolism. They play key roles in numerous diseases and are implicated in cancer progression and chemoresistance. However, the underlying mechanisms are only poorly understood. We have employed a multi-omics approach to monitor changes to gene expression after induction of a stress response pathway, the unfolded protein response (UPR), probing in parallel the transcriptome, the proteome, and changes to translation. Stringent filtering reveals the induction of 267 genes, many of which have not previously been implicated in stress response pathways. We experimentally demonstrate that UPR-mediated translational control induces the expression of enzymes involved in a pathway that diverts intermediate metabolites from glycolysis to fuel mitochondrial one-carbon metabolism. Concomitantly, the cells become resistant to the folate-based antimetabolites Methotrexate and Pemetrexed, establishing a direct link between UPR-driven changes to gene expression and resistance to pharmacological treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOPLASMIC-RETICULUM STRESS; MESSENGER-RNA TRANSLATION; MITOCHONDRIAL FOLATE; THERAPEUTIC TARGET; PATHWAY; SERINE; CANCER; EXPRESSION; REGULATOR; PROMOTES; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 07:11 |
| Last Modified: | 22 Mar 2021 07:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44402 |
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