{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ichikawa S"],"funding":["NIGMS NIH HHS"],"pagination":["775-782"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10316063"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["610(7933)"],"pubmed_abstract":["The ubiquitin E3 ligase substrate adapter cereblon (CRBN) is a target of thalidomide and lenalidomide<sup>1</sup>, therapeutic agents used in the treatment of haematopoietic malignancies<sup>2-4</sup> and as ligands for targeted protein degradation<sup>5-7</sup>. These agents are proposed to mimic a naturally occurring degron; however, the structural motif recognized by the thalidomide-binding domain of CRBN remains unknown. Here we report that C-terminal cyclic imides, post-translational modifications that arise from intramolecular cyclization of glutamine or asparagine residues, are physiological degrons on substrates for CRBN. Dipeptides bearing the C-terminal cyclic imide degron substitute for thalidomide when embedded within bifunctional chemical degraders. Addition of the degron to t"],"journal":["Nature"],"pubmed_title":["The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron."],"pmcid":["PMC10316063"],"funding_grant_id":["R01 GM114537"],"pubmed_authors":["Vallavoju N","Pratt MR","Wang B","Flaxman HA","Woo CM","Shen D","Lloyd HC","Ichikawa S","Xu W"],"additional_accession":[]},"is_claimable":false,"name":"The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron.","description":"The ubiquitin E3 ligase substrate adapter cereblon (CRBN) is a target of thalidomide and lenalidomide<sup>1</sup>, therapeutic agents used in the treatment of haematopoietic malignancies<sup>2-4</sup> and as ligands for targeted protein degradation<sup>5-7</sup>. These agents are proposed to mimic a naturally occurring degron; however, the structural motif recognized by the thalidomide-binding domain of CRBN remains unknown. Here we report that C-terminal cyclic imides, post-translational modifications that arise from intramolecular cyclization of glutamine or asparagine residues, are physiological degrons on substrates for CRBN. Dipeptides bearing the C-terminal cyclic imide degron substitute for thalidomide when embedded within bifunctional chemical degraders. Addition of the degron to t","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-05-29T09:06:00.356Z","creation":"2025-02-19T03:21:01.154Z"},"accession":"S-EPMC10316063","cross_references":{"pubmed":["36261529"],"doi":["10.1038/s41586-022-05333-5"]}}