ArticleStructure (London, England : 1993)2012
Phosphorylation regulates assembly of the caspase-6 substrate-binding groove.
Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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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
23 citing papers in PubMed, 39 citations in OpenAlex.
- The Intricate Role of Caspase-6 and Death Receptor-6 in Neurodegenerative Diseases.Cell biochemistry and biophysics · 2026Review
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- An NMR sample preparation case study: Considerations for the self-destructive protease caspase-6.PloS one · 2025Article
- The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia.Journal of animal science and biotechnology · 2024Article
- How does caspases regulation play role in cell decisions? apoptosis and beyond.Molecular and cellular biochemistry · 2024Review
- A Review on Caspases: Key Regulators of Biological Activities and Apoptosis.Molecular neurobiology · 2023Review
- Current insights in molecular characterization of non-alcoholic fatty liver disease and treatment.Frontiers in endocrinology · 2022Review
- Recent advances suggest increased influence of selective pressure in allostery.Current opinion in structural biology · 2020Review
- An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis.Science (New York, N.Y.) · 2020Article
- Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound.Cell chemical biology · 2019Article
- Identification of Allosteric Inhibitors against Active Caspase-6.Scientific reports · 2019Article
- Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity.Scientific reports · 2018Article
- Active site-adjacent phosphorylation at Tyr-397 by c-Abl kinase inactivates caspase-9.The Journal of biological chemistry · 2017Article
- Article
- Palmitoylation of caspase-6 by HIP14 regulates its activation.Cell death and differentiation · 2017Article
- Dual Site Phosphorylation of Caspase-7 by PAK2 Blocks Apoptotic Activity by Two Distinct Mechanisms.Structure (London, England : 1993) · 2017Article
- Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Reprogramming Caspase-7 Specificity by Regio-Specific Mutations and Selection Provides Alternate Solutions for Substrate Recognition.ACS chemical biology · 2016Article
- Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.Scientific reports · 2015Article
- Modifying caspase-3 activity by altering allosteric networks.Biochemistry · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Caspases, a family of apoptotic proteases, are increasingly recognized as being extensively phosphorylated, usually leading to inactivation. To date, no structural mechanism for phosphorylation-based caspase inactivation is available, although this information may be key to achieving caspase-specific inhibition. Caspase-6 has recently been implicated in neurodegenerative conditions including Huntington's and Alzheimer's diseases. A full understanding of caspase-6 regulation is crucial to caspase-6-specific inhibition. Caspase-6 is phosphorylated by ARK5 kinase at serine 257 leading to suppression of cell death via caspase-6 inhibition. Our structure of the fully inactive phosphomimetic S257D reveals that phosphorylation results in a steric clash with P201 in the L2' loop. Removal of the proline side chain alleviates the clash resulting in nearly wild-type activity levels. This phosphomimetic-mediated steric clash causes misalignment of the substrate-binding groove, preventing substrate binding. Substrate-binding loop misalignment appears to be a widely used regulatory strategy among caspases and may present a new paradigm for caspase-specific control.
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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.