ArticleCell2021
LanCLs add glutathione to dehydroamino acids generated at phosphorylated sites in the proteome.
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials.International journal of molecular sciences · 2023Pooled it
- Cyanamide-Induced Desulfhydration Enables Access to α,β-Dehydropeptides.Organic letters · 2026Article
- Lanthionine synthetase C-like protein 1 (LanCL1): a therapeutic target for neuropathic pain.Pain · 2026Article
- Experimental upregulation of Lancl1 promotes axon regeneration after optic nerve injury in vivo.Experimental neurology · 2026Article
- Loss of LanC-like proteins delays post-injury regeneration of aging skeletal muscles.bioRxiv : the preprint server for biology · 2026Article
- PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.Nature chemical biology · 2026Article
- BT-11 targets the LANCL2 pathway to attenuate cognitive deficits and hippocampal pathology in Alzheimer's transgenic rats.Scientific reports · 2025Article
- Nuclear transport of phosphorylated LanCL2 promotes invadopodia formation and tumor progression of glioblastoma by activating STAT3/Cortactin signaling.Journal of advanced research · 2025Article
- Genesis and regulation of C-terminal cyclic imides from protein damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dehydroamino acids and their crosslinks in Alzheimer's disease aggregates.Brain communications · 2025Article
- Thermal measurements support a role of the ABA/LANCL1-2 hormone/receptors system in thermogenesis.Open biology · 2024Article
- Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza.The Journal of infectious diseases · 2024Article
- The significant role of amino acid metabolic reprogramming in cancer.Cell communication and signaling : CCS · 2024Review
- Expression and Subcellular Localization of Lanthipeptides in Human Cells.ACS synthetic biology · 2024Article
- Mechanism of Abnormal Activation of MEK1 Induced by Dehydroalanine Modification.International journal of molecular sciences · 2024Article
- Insights into the production and evolution of lantibiotics from a computational analysis of peptides associated with the lanthipeptide cyclase domain.Royal Society open science · 2024Article
- Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.International journal of molecular sciences · 2024Review
- Genome Mining for New Enzyme Chemistry.ACS catalysis · 2024Review
- Late-Stage Functionalization of Living Organisms: Rethinking Selectivity in Biology.Chemical reviews · 2024Review
- Disordered regions in proteusin peptides guide post-translational modification by a flavin-dependent RiPP brominase.Nature communications · 2024Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Enzyme-mediated damage repair or mitigation, while common for nucleic acids, is rare for proteins. Examples of protein damage are elimination of phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) in pathogenesis and aging. Bacterial LanC enzymes use Dha/Dhb to form carbon-sulfur linkages in antimicrobial peptides, but the functions of eukaryotic LanC-like (LanCL) counterparts are unknown. We show that LanCLs catalyze the addition of glutathione to Dha/Dhb in proteins, driving irreversible C-glutathionylation. Chemo-enzymatic methods were developed to site-selectively incorporate Dha/Dhb at phospho-regulated sites in kinases. In human MAPK-MEK1, such "elimination damage" generated aberrantly activated kinases, which were deactivated by LanCL-mediated C-glutathionylation. Surveys of endogenous proteins bearing damage from elimination (the eliminylome) also suggest it is a source of electrophilic reactivity. LanCLs thus remove these reactive electrophiles and their potentially dysregulatory effects from the proteome. As knockout of LanCL in mice can result in premature death, repair of this kind of protein damage appears important physiologically.
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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.