ArticleNature2019
Metabolic control of BRISC-SHMT2 assembly regulates immune signalling.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 79 citations in OpenAlex.
- Oligomeric defects in soybean serine hydroxymethyltransferase 8: tetramer destabilization by A149T and other variants associated with soybean cyst nematode resistance.The FEBS journal · 2026Article
- DPP9 inhibition boosts antitumor immunity by disrupting BRISC-mediated PD-L1 expression in clear cell renal cell carcinoma.Cell death and differentiation · 2026Article
- A ubiquitin chain-feeding mechanism for BRCA1-A.Nature communications · 2026Article
- Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex.Nature communications · 2026Article
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner.Gut microbes · 2025Article
- Small-molecule glues selectively restrict deubiquitylase activity and inflammatory signaling.Nature structural & molecular biology · 2025Article
- Molecular glues that inhibit deubiquitylase activity and inflammatory signaling.Nature structural & molecular biology · 2025Article
- Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism.Discover oncology · 2025Article
- Guanine monophosphate synthase-mediated nuclear and mitochondrial communication in the progression of gastric cancer.Translational cancer research · 2025Article
- Discovery and mechanism of K63-linkage-directed deubiquitinase activity in USP53.Nature chemical biology · 2025Article
- SHMT2 modulates the transcriptome and metabolism profiles to promote the tumor phenotypes of bladder cancer HT-1376 cells.Frontiers in genetics · 2025Article
- Upregulated Expression of SHMT2 Predicts Poor Survival of Lung Adenocarcinoma.Genetics research · 2025Article
- Molecular glues that inhibit deubiquitylase activity and inflammatory signalling.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 5 countries.
Funding
Abstract
Serine hydroxymethyltransferase 2 (SHMT2) regulates one-carbon transfer reactions that are essential for amino acid and nucleotide metabolism, and uses pyridoxal-5'-phosphate (PLP) as a cofactor. Apo SHMT2 exists as a dimer with unknown functions, whereas PLP binding stabilizes the active tetrameric state. SHMT2 also promotes inflammatory cytokine signalling by interacting with the deubiquitylating BRCC36 isopeptidase complex (BRISC), although it is unclear whether this function relates to metabolism. Here we present the cryo-electron microscopy structure of the human BRISC-SHMT2 complex at a resolution of 3.8 Å. BRISC is a U-shaped dimer of four subunits, and SHMT2 sterically blocks the BRCC36 active site and inhibits deubiquitylase activity. Only the inactive SHMT2 dimer-and not the active PLP-bound tetramer-binds and inhibits BRISC. Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli. Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses. These data reveal a mechanism in which metabolites regulate deubiquitylase activity and inflammatory signalling.
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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.