GSK3α Regulates Temporally Dynamic Changes in Ribosomal Proteins upon Amino Acid Starvation in Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Loss of GSK3α Induces Asparaginase Cytotoxicity Independent from ASNS Expression in Resistant Cancer Cells
2.2. GSK3α-Mediated Response to Chronic Amino Acid Deprivation Is Independent of the GCN2-CHOP Axis
2.3. Cell Death upon Inhibition of GSK3α Is Not Mediated by Changes in Cell Cycle
2.4. Inhibition of GSK3α Leads to Temporally Dynamic Downregulation of Distinct Ribosomal Proteins in the Presence of Asparagine Deprivation
2.5. Inhibition of Specific Ribosomal Proteins Promotes Cellular Fitness upon GSK3α Inhibition and Asparagine Starvation
3. Discussion
4. Materials and Methods
4.1. Cell Lines, Cell Culture, and Organoids
4.2. Lentiviral Transduction
4.3. Short Hairpin RNA (shRNA), Single-Guide RNA (sgRNA), and Expression Plasmids
4.4. Assessment of Chemotherapy Response
4.5. Quantitative Reverse Transcriptase PCR (qRT-PCR)
4.6. Western Blot Analysis
4.7. Cell Cycle Analysis
4.8. Caspase 3/7 Activity and BH3 Profiling
4.9. Timeseries RNA Sequencing and Bioinformatic Analysis
4.10. Organoids RNA Sequencing and Bioinformatic Analysis
4.11. CRISPR/Cas9 Loss of Function Screen
4.12. Quantification and Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Loxha, L.; Ibrahim, N.K.; Stasche, A.S.; Cinar, B.; Dolgner, T.; Niessen, J.; Schreek, S.; Fehlhaber, B.; Forster, M.; Stanulla, M.; et al. GSK3α Regulates Temporally Dynamic Changes in Ribosomal Proteins upon Amino Acid Starvation in Cancer Cells. Int. J. Mol. Sci. 2023, 24, 13260. https://doi.org/10.3390/ijms241713260
Loxha L, Ibrahim NK, Stasche AS, Cinar B, Dolgner T, Niessen J, Schreek S, Fehlhaber B, Forster M, Stanulla M, et al. GSK3α Regulates Temporally Dynamic Changes in Ribosomal Proteins upon Amino Acid Starvation in Cancer Cells. International Journal of Molecular Sciences. 2023; 24(17):13260. https://doi.org/10.3390/ijms241713260
Chicago/Turabian StyleLoxha, Lorent, Nurul Khalida Ibrahim, Anna Sophie Stasche, Büsra Cinar, Tim Dolgner, Julia Niessen, Sabine Schreek, Beate Fehlhaber, Michael Forster, Martin Stanulla, and et al. 2023. "GSK3α Regulates Temporally Dynamic Changes in Ribosomal Proteins upon Amino Acid Starvation in Cancer Cells" International Journal of Molecular Sciences 24, no. 17: 13260. https://doi.org/10.3390/ijms241713260