{"doi":"10.1038/s42003-020-01240-5","title":"An IMiD-induced SALL4 degron system for selective degradation of target proteins","abstract":"<jats:title>Abstract</jats:title><jats:p>Regulating the amount of proteins in living cells is a powerful approach for understanding the functions of the proteins. Immunomodulatory drugs (IMiDs) induce the degradation of neosubstrates by interacting with celebron (CRBN) in the cullin E3 ubiquitin ligase complex (CRL4<jats:sup>CRBN</jats:sup>). Here, we developed the IMiD-dependent Sal-like protein 4 (SALL4) degron (S4D) system for chemical protein knockdown. In transient assays, an N- or C-terminal S4D tag induced the degradation of proteins localized to various subcellular compartments, including the plasma membrane. The activity of luciferase-S4D was reduced by 90% within 3 h of IMiD treatment. IMiD treatment reduced the expression of endogenous S4D-fused RelA and IκBα in knock-in (KI) experiments. Interestingly, the IκBα knockdown suggested that there may be another, unknown mechanism for RelA translocation to the nucleus. Furthermore, 5-hydroxythalidomide as a thalidomide metabolite specifically degradated S4D-tagged protein. These results indicate that the S4D system is a useful tool for cellular biology.</jats:p>","journal":"Communications Biology","year":2020,"id":648023,"datarank":1.2294970932157554,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.7096367077957964,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.7096367077957964,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":26,"citers_with_citation_signal":23,"citers_with_endowment":23,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1688560,"name":"Yuki Shoya","orcid":null,"position":1,"is_corresponding":false},{"id":1688563,"name":"Saya Matsuoka","orcid":null,"position":2,"is_corresponding":false},{"id":935067,"name":"Hisayo Nishida‐Fukuda","orcid":"0000-0002-4661-779X","position":3,"is_corresponding":false},{"id":1688567,"name":"Norio Shibata","orcid":"0000-0002-3742-4064","position":4,"is_corresponding":false},{"id":114529,"name":"Tatsuya Sawasaki","orcid":"0000-0002-7952-0556","position":5,"is_corresponding":false},{"id":1688557,"name":"Satoshi Yamanaka","orcid":"0000-0001-8825-7481","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An IMiD-induced SALL4 degron system for selective degradation of target proteins","abstract":"<jats:title>Abstract</jats:title><jats:p>Regulating the amount of proteins in living cells is a powerful approach for understanding the functions of the proteins. Immunomodulatory drugs (IMiDs) induce the degradation of neosubstrates by interacting with celebron (CRBN) in the cullin E3 ubiquitin ligase complex (CRL4<jats:sup>CRBN</jats:sup>). Here, we developed the IMiD-dependent Sal-like protein 4 (SALL4) degron (S4D) system for chemical protein knockdown. In transient assays, an N- or C-terminal S4D tag induced the degradation of proteins localized to various subcellular compartments, including the plasma membrane. The activity of luciferase-S4D was reduced by 90% within 3 h of IMiD treatment. IMiD treatment reduced the expression of endogenous S4D-fused RelA and IκBα in knock-in (KI) experiments. Interestingly, the IκBα knockdown suggested that there may be another, unknown mechanism for RelA translocation to the nucleus. Furthermore, 5-hydroxythalidomide as a thalidomide metabolite specifically degradated S4D-tagged protein. 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