{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:23:51Z","timestamp":1789903431543,"version":"4.0.1"},"reference-count":70,"publisher":"American Society for Cell Biology (ASCB)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>A pathway for cystic fibrosis transmembrane conductance regulator (CFTR) degradation is initiated by Hsp27, which cooperates with Ubc9 and binds to the common F508del mutant to modify it with SUMO-2\/3. These SUMO paralogues form polychains, which are recognized by the ubiquitin ligase, RNF4, for proteosomal degradation. Here, protein array analysis identified the SUMO E3, protein inhibitor of activated STAT 4 (PIAS4), which increased wild-type (WT) and F508del CFTR biogenesis in CFBE airway cells. PIAS4 increased immature CFTR threefold and doubled expression of mature CFTR, detected by biochemical and functional assays. In cycloheximide chase assays, PIAS4 slowed immature F508del degradation threefold and stabilized mature WT CFTR at the plasma membrance. PIAS4 knockdown reduced WT and F508del CFTR expression by 40\u201350%, suggesting a physiological role in CFTR biogenesis. PIAS4 modified F508del CFTR with SUMO-1 in vivo and reduced its conjugation to SUMO-2\/3. These SUMO paralogue-specific effects of PIAS4 were reproduced in vitro using purified F508del nucleotide-binding domain 1 and SUMOylation reaction components. PIAS4 reduced endogenous ubiquitin conjugation to F508del CFTR by \u223c50% and blocked the impact of RNF4 on mutant CFTR disposal. These findings indicate that different SUMO paralogues determine the fates of WT and mutant CFTRs, and they suggest that a paralogue switch during biogenesis can direct these proteins to different outcomes: biogenesis versus degradation.<\/jats:p>","DOI":"10.1091\/mbc.e18-04-0252","type":"journal-article","created":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T14:14:16Z","timestamp":1541600056000},"page":"4-16","source":"Crossref","is-referenced-by-count":19,"title":["Different SUMO paralogues determine the fate of wild-type and mutant CFTRs: biogenesis versus degradation"],"prefix":"10.1091","volume":"30","author":[{"given":"Xiaoyan","family":"Gong","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liao","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Cell Biology, 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