ArticleProceedings of the National Academy of Sciences of the United States of America2017
p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 87 citations in OpenAlex.
- Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.eLife · 2026Article
- Proteomic Analysis Reveals That P97 Inhibitors Induce Ferroptosis in Gastric Cancer AGS Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Syringin disrupts the DLAT/MYC axis to dampen TAM polarization and suppress hepatocellular carcinoma progression.Acta pharmaceutica Sinica. B · 2026Article
- Expression of LIFR in tumor and SHOC2, YAP1 in plasma mRNA as potential biomarkers in KRASScientific reports · 2026Article
- Targeting VCP enhances colorectal cancer therapy through STING stabilization.Journal for immunotherapy of cancer · 2025Article
- VCP Promotes Cholangiocarcinoma Development by Mediating BAP1 Ubiquitination-Dependent Degradation.Cancer science · 2025Article
- Cellular parameters shaping pathways of targeted protein degradation.Communications biology · 2025Review
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- CRBN modulates synuclein fibrillation via degradation of DNAJB1 in mouse model of Parkinson disease.NPJ Parkinson's disease · 2024Article
- Intrinsic signaling pathways modulate targeted protein degradation.Nature communications · 2024Article
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells.Nature communications · 2024Article
- Article
- USP28 promotes tumorigenesis and cisplatin resistance by deubiquitinating MAST1 protein in cancer cells.Cellular and molecular life sciences : CMLS · 2024Article
- GLUL stabilizes N-Cadherin by antagonizingActa pharmaceutica Sinica. B · 2024Article
- The CRL3Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Nuclear VCP drives colorectal cancer progression by promoting fatty acid oxidation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.Experimental & molecular medicine · 2023Article
- Review
- CRISPR/Cas9-based genome-wide screening of the deubiquitinase subfamily identifies USP3 as a protein stabilizer of REST blocking neuronal differentiation and promotes neuroblastoma tumorigenesis.Journal of experimental & clinical cancer research : CR · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function. Notably, p97 is also required for the degradation of all four known CRBN neo-substrates [Ikaros family zinc finger proteins 1 (IKZF1) and 3 (IKZF3), casein kinase 1α (CK1α), and the translation termination factor GSPT1] whose ubiquitylation is induced by immunomodulatory drugs. Together, these data point to an unexpectedly intimate relationship between the E3 ubiquitin ligase CRL4
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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.