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Thus, the UPS is properly regulated. Here we show novel UPS-related factors: the fragile X mental retardation 1 (FMR1) and Fmr1 autosomal homolog 1 (FXR1) proteins and <jats:italic>discs large MAGUK scaffold protein 4<\/jats:italic> (<jats:italic>Dlg4<\/jats:italic>) mRNA, which are associated with Fragile X syndrome, are involved in UPS activity. <jats:italic>Fmr1<\/jats:italic>-, <jats:italic>Fxr1<\/jats:italic>- and <jats:italic>Dlg4<\/jats:italic>-knockdown and <jats:italic>Fmr1<\/jats:italic>- and <jats:italic>Fxr1<\/jats:italic>-knockdown resulted in increased ubiquitination and proteasome activity, respectively. FXR1 protein was further confirmed to be associated with proteasomes, and <jats:italic>Dlg4<\/jats:italic> mRNA itself was found to be involved in the UPS. Knockdown of these genes also affected neurite outgrowth. These findings provide new insights into the regulatory mechanism of the UPS and into the interpretation of the pathogenesis of diseases in which these genes are involved as UPS-related factors.<\/jats:p>","DOI":"10.1038\/s41598-023-29152-4","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T17:04:52Z","timestamp":1675357492000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["FMRP, FXR1 protein and Dlg4 mRNA, which are associated with fragile X syndrome, are involved in the ubiquitin\u2013proteasome system"],"prefix":"10.1038","volume":"13","author":[{"given":"Hideo","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Hohjoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"29152_CR1","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<442::AID-BIES6>3.0.CO;2-Q","volume":"22","author":"A Ciechanover","year":"2000","unstructured":"Ciechanover, A., Orian, A. & Schwartz, A. 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