Genome-wide CRISPR screen reveals genetic modifiers of Ca2+-mediated cell death
Reyes Gaido, O. E.; Schole, K. L.; Anderson, M. E.; Luczak, E. D.
Show abstract
Ca2+ is a fundamental determinant of survival in living cells. Excessive intracellular Ca2+ causes cellular toxicity and death but the genetic pathways contributing to Ca2+ induced cell death are incompletely understood. Here, we performed genome-wide CRISPR knock-out screening in human cells challenged with the Ca2+ ionophore ionomycin and identified genes and pathways essential for cell death after Ca2+ overload. We discovered 115 protective gene knockouts, 82 of which are non-essential genes and 21 of which belong to the druggable genome. Notably, members of store operated Ca2+ entry (SOCE), very long-chain fatty acid synthesis, and SWItch/Sucrose Non-Fermentable (SWI/SNF) pathways provided marked protection against Ca2+ toxicity. These results reveal pathways previously unknown to mediate Ca2+-induced cell death and provide a resource for the development of pharmacotherapies against the sequelae of Ca2+ overload in disease.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genome-wide CRISPR screens reveal multitiered mechanisms through which mTORC1 senses mitochondrial dysfunction 96%
- Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production 95%
- Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice 95%
Similar papers in this journal
- Protein proximity networks and functional evaluation of the Casein Kinase 1 γ family reveals unique roles for CK1γ3 in WNT signaling 94%
- The METTL5-TRMT112 N6-methyladenosine methyltransferase complex regulates metabolism and development via translation 94%
- Up-regulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain 94%
Similar papers in this journal
- Mitochondrial respiration contributes to the interferon gamma response in antigen presenting cells 95%
- Combinatorial CRISPR screen reveals FYN and KDM4 as targets for synergistic drug combination for treating triple negative breast cancer 95%
- An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput screens 95%
Similar papers in this journal
- Simultaneous inhibition of DNA-PK and Pol{Theta} improves integration efficiency and precision of genome editing 95%
- Citrullination of pyruvate kinase by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation. 95%
- Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.