ArticleMolecular cell2024
Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Charged molecular glue discovery enabled by targeted degron display.Nature chemical biology · 2026Article
- Ubiquitylation by the GID/CTLH complex regulates the metabolic and innate immune response of macrophages to infection by Mycobacterium tuberculosis.PLoS pathogens · 2026Article
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Beyond Taxonomy: A Matrix-Trait-Function Framework for Predictive Selection of Non-Microorganisms · 2026Review
- Wdr26 insufficiency causes Skraban-Deardorff syndrome-like neurodevelopmental deficits in mice.The Journal of clinical investigation · 2026Article
- Article
- Ypel5 preserves female fertility by regulating folliculogenesis and oocyte maturation.Cell death and differentiation · 2026Article
- GID/CTLH E3 ligase complex control cell fate programs for sexual development of Plasmodium falciparum.Nature communications · 2026Article
- Article
- Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Loss of RanBP9 cooperates with p53 deficiency to promote sarcomagenesis.Frontiers in oncology · 2026Article
- Blocking Lysine Crotonylation and Aerobic Glycolysis as Targeting Strategy Against mpox Virus Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The CTLH ubiquitin ligase substrates ZMYND19 and MKLN1 negatively regulate mTORC1 at the lysosomal membrane.Nature communications · 2025Article
- The many faces of the GID/CTLH E3 ligase complex.Biochemical Society transactions · 2025Review
- MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The generation and consequences of N-terminal proteoform diversity.Cell reports · 2025Review
- Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation.Nature structural & molecular biology · 2025Article
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
- RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.Journal of experimental & clinical cancer research : CR · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic enzyme substrates. The orthologous higher eukaryotic C-terminal to LisH (CTLH) E3 complex has been proposed to also recognize substrates through an alternative subunit, WDR26, which promotes the formation of supramolecular CTLH E3 assemblies. Here, we discover that human WDR26 binds the metabolic enzyme nicotinamide/nicotinic-acid-mononucleotide-adenylyltransferase 1 (NMNAT1) and mediates its CTLH E3-dependent ubiquitylation independently of canonical GID/CTLH E3-family substrate receptors. The CTLH subunit YPEL5 inhibits NMNAT1 ubiquitylation and cellular turnover by WDR26-CTLH E3, thereby affecting NMNAT1-mediated metabolic activation and cytotoxicity of the prodrug tiazofurin. Cryoelectron microscopy (cryo-EM) structures of NMNAT1- and YPEL5-bound WDR26-CTLH E3 complexes reveal an internal basic degron motif of NMNAT1 essential for targeting by WDR26-CTLH E3 and degron mimicry by YPEL5's N terminus antagonizing substrate binding. Thus, our data provide a mechanistic understanding of how YPEL5-WDR26-CTLH E3 acts as a modulator of NMNAT1-dependent metabolism.
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