ArticleProceedings of the National Academy of Sciences of the United States of America2017
Structural basis of autoregulatory scaffolding by apoptosis signal-regulating kinase 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The Association Between Serum Gamma-Glutamyl Transferase and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.Cancer medicine · 2025Pooled it
- Review
- Review
- c-Jun in neurodegeneration: A key transcriptional regulator with therapeutic implications.Molecular therapy. Nucleic acids · 2026Review
- Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise.Apoptosis : an international journal on programmed cell death · 2025Review
- Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.Molecular and cellular biochemistry · 2025Review
- The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1.eLife · 2024Article
- Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.Frontiers in cell and developmental biology · 2024Review
- The Function of ASK1 in Sepsis and Stress-Induced Disorders.International journal of molecular sciences · 2023Review
- MAPK Signaling Pathways in Hepatic Ischemia/Reperfusion Injury.Journal of inflammation research · 2023Review
- Intrinsic disorder in proteins associated with oxidative stress-induced JNK signaling.Cellular and molecular life sciences : CMLS · 2022Article
- Crystallographic mining of ASK1 regulators to unravel the intricate PPI interfaces for the discovery of small molecule.Computational and structural biotechnology journal · 2022Review
- Structural Insights Support Targeting ASK1 Kinase for Therapeutic Interventions.International journal of molecular sciences · 2021Review
- Prdx1 Interacts with ASK1 upon Exposure to HAntioxidants (Basel, Switzerland) · 2021Article
- Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways.Cell death & disease · 2021Article
- The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases.International journal of molecular sciences · 2020Review
- Identification of Uncharacterized Components of Prokaryotic Immune Systems and Their Diverse Eukaryotic Reformulations.Journal of bacteriology · 2020Article
- BAK core dimers bind lipids and can be bridged by them.Nature structural & molecular biology · 2020Article
- TheProceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Regulation of JNK Signaling Pathways in Cell Death through the Interplay with Mitochondrial SAB and Upstream Post-Translational Effects.International journal of molecular sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis signal-regulating kinases (ASK1-3) are apical kinases of the p38 and JNK MAP kinase pathways. They are activated by diverse stress stimuli, including reactive oxygen species, cytokines, and osmotic stress; however, a molecular understanding of how ASK proteins are controlled remains obscure. Here, we report a biochemical analysis of the ASK1 kinase domain in conjunction with its N-terminal thioredoxin-binding domain, along with a central regulatory region that links the two. We show that in solution the central regulatory region mediates a compact arrangement of the kinase and thioredoxin-binding domains and the central regulatory region actively primes MKK6, a key ASK1 substrate, for phosphorylation. The crystal structure of the central regulatory region reveals an unusually compact tetratricopeptide repeat (TPR) region capped by a cryptic pleckstrin homology domain. Biochemical assays show that both a conserved surface on the pleckstrin homology domain and an intact TPR region are required for ASK1 activity. We propose a model in which the central regulatory region promotes ASK1 activity via its pleckstrin homology domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding and kinase domains into close proximity. Such an architecture provides a mechanism for control of ASK-type kinases by diverse activators and inhibitors and demonstrates an unexpected level of autoregulatory scaffolding in mammalian stress-activated MAP kinase signaling.
Indexed as
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.