ReviewThe Biochemical journal2019
Resurrection of ancestral effector caspases identifies novel networks for evolution of substrate specificity.
Review in The Biochemical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 26 citations in OpenAlex.
- Evolution of the conformational ensemble and allosteric networks of apoptotic caspases in chordates.The Biochemical journal · 2025Article
- Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease.Cell discovery · 2025Review
- Cholesterol, Eukaryotic Lipid Domains, and an Evolutionary Perspective of Transmembrane Signaling.Cold Spring Harbor perspectives in biology · 2023Review
- Sequential Unfolding Mechanisms of Monomeric Caspases.Biochemistry · 2023Article
- Sequential unfolding mechanisms of monomeric caspases.bioRxiv : the preprint server for biology · 2023Article
- The roles of ERIANIN in tumor and innate immunity and its' perspectives in immunotherapy.Frontiers in immunology · 2023Review
- Comparing the folding landscapes of evolutionarily divergent procaspase-3.Bioscience reports · 2022Article
- Resurrection of an ancient inflammatory locus reveals switch to caspase-1 specificity on a caspase-4 scaffold.The Journal of biological chemistry · 2022Article
- Non-Apoptotic Caspase Activity Preferentially Targets a Novel Consensus Sequence Associated With Cytoskeletal Proteins in the Developing Auditory Brainstem.Frontiers in cell and developmental biology · 2022Article
- Evolution of the folding landscape of effector caspases.The Journal of biological chemistry · 2021Article
- Article
- Great balls of fire: activation and signalling of inflammatory caspases.Biochemical Society transactions · 2021Review
- Caspases from scleractinian coral show unique regulatory features.The Journal of biological chemistry · 2020Article
- Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences.Nucleic acids research · 2020Review
- Novel Apoptotic Mediators Identified by Conservation of Vertebrate Caspase Targets.Biomolecules · 2020Article
- Evodiamine suppresses the progression of non-small cell lung carcinoma via endoplasmic reticulum stress-mediated apoptosis pathwayInternational journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Apoptotic caspases evolved with metazoans more than 950 million years ago (MYA), and a series of gene duplications resulted in two subfamilies consisting of initiator and effector caspases. The effector caspase genes (caspases-3, -6, and -7) were subsequently fixed into the Chordata phylum more than 650 MYA when the gene for a common ancestor (CA) duplicated, and the three effector caspases have persisted throughout mammalian evolution. All caspases prefer an aspartate residue at the P1 position of substrates, so each caspase evolved discrete cellular roles through changes in substrate recognition at the P4 position combined with allosteric regulation. We examined the evolution of substrate specificity in caspase-6, which prefers valine at the P4 residue, compared with caspases-3 and -7, which prefer aspartate, by reconstructing the CA of effector caspases (AncCP-Ef1) and the CA of caspase-6 (AncCP-6An). We show that AncCP-Ef1 is a promiscuous enzyme with little distinction between Asp, Val, or Leu at P4. The specificity of caspase-6 was defined early in its evolution, where AncCP-6An demonstrates a preference for Val over Asp at P4. Structures of AncCP-Ef1 and of AncCP-6An show a network of charged amino acids near the S4 pocket that, when combined with repositioning a flexible active site loop, resulted in a more hydrophobic binding pocket in AncCP-6An. The ancestral protein reconstructions show that the caspase-hemoglobinase fold has been conserved for over 650 million years and that only three substitutions in the scaffold are necessary to shift substrate selection toward Val over Asp.
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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.