ArticleNature chemical biology2026
PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.
Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Aspartimide Modification in RiPP Natural Products.Biochemistry · 2026Review
- Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry.Nature structural & molecular biology · 2026Article
- Clues for glues: from serendipity to nature's blueprints in degrader discovery.Essays in biochemistry · 2025Review
- A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation.Nature communications · 2025Article
- A method for the detection and enrichment of endogenous cereblon substrates.Cell chemical biology · 2025Article
- Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.bioRxiv : the preprint server for biology · 2025Article
- A method for the detection and enrichment of endogenous cereblon substrates.bioRxiv : the preprint server for biology · 2025Article
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Abstract
The E3 ligase substrate adapter cereblon (CRBN), the primary target of clinical agents thalidomide and lenalidomide, recognizes endogenous substrates bearing the C-terminal cyclic imide modification. Although C-terminal cyclic imides can form spontaneously, an enzyme that regulates their formation and thereby promotes a biological pathway connecting substrates to CRBN is unknown. Here we report that protein carboxymethyltransferase (PCMT1) promotes formation of C-terminal cyclic imides on C-terminal asparagine residues of CRBN substrates. PCMT1 and CRBN coregulate the levels of metabolic enzymes including glutamine synthetase and inorganic pyrophosphatase 1 in vitro, in cells and in vivo, and this regulation is associated with the proepileptic phenotype of CRBN knockout mouse models. The discovery of an enzyme that regulates CRBN substrates through the C-terminal cyclic imide reveals a previously unknown biological pathway that is perturbed by thalidomide derivatives and provides a biochemical basis for the connection between multiple biological processes and CRBN.
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