ArticleeLife2015
Unravelling druggable signalling networks that control F508del-CFTR proteostasis.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Integrative genomic meta-analysis reveals novel molecular insights into cystic fibrosis and ΔF508-CFTR rescue.Scientific reports · 2020Pooled it
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- Machine-learning repurposing of DrugBank compounds for opioid use disorder.Computers in biology and medicine · 2023Article
- Distinct proteostasis states drive pharmacologic chaperone susceptibility for cystic fibrosis transmembrane conductance regulator misfolding mutants.Molecular biology of the cell · 2022Article
- Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform.CPT: pharmacometrics & systems pharmacology · 2022Article
- Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021Review
- Review
- Proteostasis regulators modulate proteasomal activity and gene expression to attenuate multiple phenotypes in Fabry disease.The Biochemical journal · 2020Article
- Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure.Molecular diagnosis & therapy · 2019Review
- Drug repurposing: progress, challenges and recommendations.Nature reviews. Drug discovery · 2019Review
- Structure-guided combination therapy to potently improve the function of mutant CFTRs.Nature medicine · 2018Article
- Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase.Developmental cell · 2018Article
- Peripheral Protein Quality Control as a Novel Drug Target for CFTR Stabilizer.Frontiers in pharmacology · 2018Review
- Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis.Nature medicine · 2017Article
- CFTR pharmacology.Cellular and molecular life sciences : CMLS · 2017Review
- Identification of p38 MAPK and JNK as new targets for correction of Wilson disease-causing ATP7B mutants.Hepatology (Baltimore, Md.) · 2016Article
- CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis.Frontiers in pharmacology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis (CF) is caused by mutations in CF transmembrane conductance regulator (CFTR). The most frequent mutation (F508del-CFTR) results in altered proteostasis, that is, in the misfolding and intracellular degradation of the protein. The F508del-CFTR proteostasis machinery and its homeostatic regulation are well studied, while the question whether 'classical' signalling pathways and phosphorylation cascades might control proteostasis remains barely explored. Here, we have unravelled signalling cascades acting selectively on the F508del-CFTR folding-trafficking defects by analysing the mechanisms of action of F508del-CFTR proteostasis regulator drugs through an approach based on transcriptional profiling followed by deconvolution of their gene signatures. Targeting multiple components of these signalling pathways resulted in potent and specific correction of F508del-CFTR proteostasis and in synergy with pharmacochaperones. These results provide new insights into the physiology of cellular proteostasis and a rational basis for developing effective pharmacological correctors of the F508del-CFTR defect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.