ArticleMolecular cell2016
Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 176 citations in OpenAlex.
- Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.eLife · 2026Article
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Review
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.Nature chemical biology · 2026Article
- Cereblon enhances hepatic hepcidin production through estrogen-related receptor gamma activation.BMB reports · 2026Article
- Targeted recruitment of USP15 enhances CTLA4 surface levels and restricts its degradation.Life science alliance · 2026Article
- Cereblon (CRBN) inhibits prostate cancer metastasis by negatively regulating 6-phosphogluconate dehydrogenase (6PGD).Oncogene · 2026Article
- A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation.Nature communications · 2025Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Expanding the clinical and genetic spectrum of GLUL-related developmental and epileptic encephalopathy.Scientific reports · 2025Article
- A method for the detection and enrichment of endogenous cereblon substrates.Cell chemical biology · 2025Article
- D-2HG Inhibits Glutamine Synthetase Activity and Induces Senescence in IDH-Mutant Gliomas.Aging and disease · 2025Article
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Acetylation: a new target for protein degradation in cancer.Trends in cancer · 2025Review
- A method for the detection and enrichment of endogenous cereblon substrates.bioRxiv : the preprint server for biology · 2025Article
- Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome.Cell communication and signaling : CCS · 2025Article
- Oncogenic Control of Metabolism.Cold Spring Harbor perspectives in medicine · 2024Review
- Enhanced homeostatic sleep response and decreased neurodegenerative proteins in cereblon knock-out mice.Communications biology · 2024Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4(CRBN) that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation.
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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.