{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:28:01Z","timestamp":1773178081788,"version":"3.50.1"},"reference-count":59,"publisher":"American Society for Cell Biology (ASCB)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p> Protein misfolding is linked to many neurodegenerative disorders, such as Huntington's disease. The increase of glutamine-encoding CAG repeats in the first exon of huntingtin ( HTT) causes Huntington's disease. Protein fragments of Htt exon 1 with polyQ expansion (mutant HTT, mHtt) are prone to aggregation, resulting in oligomers, amyloid fibrils, or large inclusion bodies. Previous studies demonstrate mHtt SUMOylation, a process of covalent attachment of small ubiquitin-like modifiers (SUMO) to target proteins. Protein polySUMOylation further triggers its ubiquitination and segregation by the polySUMO axis. Here, we examined how SUMOylation regulates aggregation and degradation of Htt103QP-GFP, a model mHtt, in budding yeast. We first confirmed Htt103QP-GFP SUMOylation in budding yeast. We also found that recruitment of the SUMO E2-conjugating enzyme to Htt103QP-GFP accelerates its aggregation, but recruitment of a SUMO protease to Htt103QP-GFP delays this process. Disruption of the polySUMO axis led to increased Htt103QP-GFP aggregation. Interestingly, the results from fluorescence recovery after photobleaching assay and treatment with a biomolecular condensate-disrupting chemical indicate that SUMOylation accelerates biomolecular condensate formation of Htt103QP-GFP. Importantly, impaired SUMOylation delays Htt103QP-GFP proteasomal degradation and accelerates formation of SDS-insoluble Htt103QP-GFP aggregates. Together, these results indicate that SUMOylation facilitates proteasomal degradation of misfolded proteins by retaining their solubility. <\/jats:p>","DOI":"10.1091\/mbc.e24-12-0540","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:55:36Z","timestamp":1746057336000},"source":"Crossref","is-referenced-by-count":7,"title":["Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast"],"prefix":"10.1091","volume":"36","author":[{"given":"Austin","family":"Folger","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306-4300"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Gutierrez-Morton","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 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