{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:48:12Z","timestamp":1747183692191,"version":"3.40.5"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI 17K07088","JSPS KAKENHI 17K07089","JSPS KAKENHI 18H02533"],"award-info":[{"award-number":["JSPS KAKENHI 17K07088","JSPS KAKENHI 17K07089","JSPS KAKENHI 18H02533"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Posttranslational modifications by phosphorylation, ubiquitination, neddylation and other pathways have emerged as major regulators of cellular functions. NEDD8 ultimate buster 1, NUB1, is an adaptor protein, which negatively regulates the levels of the ubiquitin\u2010like protein NEDD8 as well as neddylated proteins through proteasomal degradation. We previously reported that NUB1 is highly involved in the pathogenesis of synucleinopathy including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). In general, since phosphorylation is strongly related to the alteration of protein propensity, we examined if the fundamental function of NUB1 can be modulated by its phosphorylation. We created a series of phosphomimic mutants of NUB1. Among them, we found that phosphorylation of NUB1 at S46 (P\u2010NUB46) efficiently degrades aggregates using a cell\u2010based assay. Immunohistochemical studies have shown that specific antibodies against P\u2010NUB46 reacted with Lewy bodies in PD and DLB but not with glial cytoplasmic inclusions in MSA. Moreover, P\u2010NUB46 levels were significantly higher in the brains of patients with DLB than in control brains, and P\u2010NUB46 was extracted in an insoluble fraction of DLB. These findings suggest that the phosphorylation of NUB1 is modulated during the pathological process of Lewy body disease.<\/jats:p>","DOI":"10.1111\/bpa.12728","type":"journal-article","created":{"date-parts":[[2019,4,21]],"date-time":"2019-04-21T13:43:38Z","timestamp":1555854218000},"page":"803-812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Phosphorylated NUB1 distinguishes \u03b1\u2010synuclein in Lewy bodies from that in glial cytoplasmic inclusions in multiple system atrophy"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-2215","authenticated-orcid":false,"given":"Kunikazu","family":"Tanji","sequence":"first","affiliation":[{"name":"Department of Neuropathology, Institute of Brain Science Hirosaki University Graduate School of Medicine Hirosaki 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