{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kagiou C"],"funding":["Austrian Science Fund FWF","European Research Council"],"pagination":["5409"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11208438"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCF<sup>FBXO22</sup> ligase for FKBP12 degradation. Targ"],"journal":["Nature communications"],"pubmed_title":["Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation."],"pmcid":["PMC11208438"],"funding_grant_id":["851478","P5918723","789016","P7909","P36746"],"pubmed_authors":["Scholes NS","Hannich JT","Kubicek S","Yang K","Farnung J","Offensperger F","Cisneros JA","Liwocha J","Tin G","Sanchez Avila J","Kagiou C","Zuber J","Dong K","Paulo JA","Horstmann CS","Andersch F","Gygi SP","Schulman BA","Winter GE","Hinterndorfer M","Fellner M"],"additional_accession":[]},"is_claimable":false,"name":"Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation.","description":"Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCF<sup>FBXO22</sup> ligase for FKBP12 degradation. Targ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2025-04-04T21:22:21.731Z","creation":"2025-04-04T21:22:21.731Z"},"accession":"S-EPMC11208438","cross_references":{"pubmed":["38926334"],"doi":["10.1038/s41467-024-49739-3"]}}