{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hoing S"],"funding":["CRTD","Deutsche Forschungsgemeinschaft","NINDS NIH HHS","Max Planck Society","NIGMS NIH HHS","Krieger School of Arts & Sciences, Johns Hopkins University","Cluster of Excellence"],"pagination":["357-369.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8543760"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(4)"],"pubmed_abstract":["Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh signaling downstream of Smo are urgently needed. We identified dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly to inhibit cytoplasmic dynein 1-dependent microtubule binding and motility in vitro without affecting ATP hydrolysis. It rapidly and reversibly inhibits endosome movement in living cells and perturbs mitosis by inducing spindle misorientation and pseudoprometaphase delay. Dynarrestin reversibly inhibits cytoplasmic dynein 2-dependent intraflagellar transport (IFT) of the cargo IFT88 and flux of Smo within cilia without interf"],"journal":["Cell chemical biology"],"pubmed_title":["Dynarrestin, a Novel Inhibitor of Cytoplasmic Dynein."],"pmcid":["PMC8543760"],"funding_grant_id":["R01 NS048501","DFG EXC 168","R56 GM044589","DFG FZ 111","R01 GM044589"],"pubmed_authors":["Waldmann H","Scholer HR","Reinhardt L","Klebl B","Baumann M","Martinez NE","Kremer L","Drexler HCA","Nussbaumer P","Ketcham SA","Abo-Rady M","Nandini S","Ziegler S","Schroer TA","Zischinsky G","Kuchler P","Habenberger P","Choidas A","Hoing S","Sterneckert J","Reinhardt P","Zischinsky ML","Yeh TY","Glatza M","Ledray AP","King SJ"],"additional_accession":[]},"is_claimable":false,"name":"Dynarrestin, a Novel Inhibitor of Cytoplasmic Dynein.","description":"Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh signaling downstream of Smo are urgently needed. We identified dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly to inhibit cytoplasmic dynein 1-dependent microtubule binding and motility in vitro without affecting ATP hydrolysis. It rapidly and reversibly inhibits endosome movement in living cells and perturbs mitosis by inducing spindle misorientation and pseudoprometaphase delay. Dynarrestin reversibly inhibits cytoplasmic dynein 2-dependent intraflagellar transport (IFT) of the cargo IFT88 and flux of Smo within cilia without interf","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Apr","modification":"2025-04-04T02:04:26.22Z","creation":"2025-02-18T23:55:41.065Z"},"accession":"S-EPMC8543760","cross_references":{"pubmed":["29396292"],"doi":["10.1016/j.chembiol.2017.12.014"]}}