ArticleCell systems2016
Network Architecture Predisposes an Enzyme to Either Pharmacologic or Genetic Targeting.
Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Nicotinamide N-methyltransferase (NNMT) regulates the glucocorticoid signaling pathway during the early phase of adipogenesis.Scientific reports · 2023Article
- Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular CaInternational journal of molecular sciences · 2022Article
- Cellular mechanism of action of 2-nitroimidazoles as hypoxia-selective therapeutic agents.Redox biology · 2022Article
- CRISPR guides induce gene silencing in plants in the absence of Cas.Genome biology · 2022Article
- Article
- Tuberculosis drug discovery in the CRISPR era.PLoS pathogens · 2019Article
- A system-wide network reconstruction of gene regulation and metabolism in Escherichia coli.PLoS computational biology · 2019Article
- Dual-specificity phosphatase 5 controls the localized inhibition, propagation, and transforming potential of ERK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Systems Approaches to Cancer Biology.Cancer research · 2016Article
- Article
- Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Chemical inhibition and genetic knockdown of enzymes are not equivalent in cells, but network-level mechanisms that cause discrepancies between knockdown and inhibitor perturbations are not understood. Here we report that enzymes regulated by negative feedback are robust to knockdown but susceptible to inhibition. Using the Raf-MEK-ERK kinase cascade as a model system, we find that ERK activation is resistant to genetic knockdown of MEK but susceptible to a comparable degree of chemical MEK inhibition. We demonstrate that negative feedback from ERK to Raf causes this knockdown-versus-inhibitor discrepancy in vivo. Exhaustive mathematical modeling of three-tiered enzyme cascades suggests that this result is general: negative autoregulation or feedback favors inhibitor potency, whereas positive autoregulation or feedback favors knockdown potency. Our findings provide a rationale for selecting pharmacologic versus genetic perturbations in vivo and point out the dangers of using knockdown approaches in search of drug targets.
Identifiers
What OpenQuestion holds
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.