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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\u2009h of IMiD treatment. IMiD treatment reduced the expression of endogenous S4D-fused RelA and I\u03baB\u03b1 in knock-in (KI) experiments. Interestingly, the I\u03baB\u03b1 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>","DOI":"10.1038\/s42003-020-01240-5","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T10:15:41Z","timestamp":1600424141000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["An IMiD-induced SALL4 degron system for selective degradation of target proteins"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8825-7481","authenticated-orcid":false,"given":"Satoshi","family":"Yamanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Shoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saya","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-779X","authenticated-orcid":false,"given":"Hisayo","family":"Nishida-Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-4064","authenticated-orcid":false,"given":"Norio","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-0556","authenticated-orcid":false,"given":"Tatsuya","family":"Sawasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"1240_CR1","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.cell.2006.08.023","volume":"126","author":"MA Lampson","year":"2006","unstructured":"Lampson, M. 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