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Here we used real-time live cell microscopy and biochemical assays to show that the primordial dwarfism (PD)-related cysteine-rich protein CRIPT dictates the spindle disassembly in a redox-dependent manner in human cells. This previously reported cytoplasmic protein was found to have a confined nuclear localization with a nucleolar concentration during interphase but was distributed to spindles and underwent redox modifications to form disulfide bonds in CXXC pairs during mitosis. Then, it directly interacted with, and might transfer a redox response to, tubulin subunits via a putative redox exchange among cysteine residues to induce microtubule depolymerization. Expression of CRIPT proteins with mutations of these cysteine residues blocked spindle disassembly, generating two cell types with long-lasting metaphase spindles or spindle remnants. Live-cell recordings of a disease-relevant mutant (CRIPTC3Y) revealed that microtubule depolymerization at spindle ends during anaphase and the entire spindle dissolution during telophase might share a common CRIPT-bearing redox-controlled mechanism.<\/jats:p>","DOI":"10.1242\/jcs.259657","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T08:59:27Z","timestamp":1663923567000},"source":"Crossref","is-referenced-by-count":2,"title":["Mitotic spindle disassembly in human cells relies on CRIPT having hierarchical redox signals"],"prefix":"10.1242","volume":"135","author":[{"given":"Kehan","family":"Xu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-5533","authenticated-orcid":false,"given":"Kari","family":"Kein\u00e4nen","sequence":"additional","affiliation":[{"name":"University of Helsinki 2 Research Program in Molecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences , , Helsinki 00014 , Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-1774","authenticated-orcid":false,"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , China"},{"name":"Yale University School of Medicine 3 Department of Neuroscience , , New Haven, CT 06510 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0994-7511","authenticated-orcid":false,"given":"Chunlin","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , China"},{"name":"Anhui Duoneng Biotechnology Co., Ltd. 4 , Hefei, Anhui 230088 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"2022092808594342600_JCS259657C1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/biology6010015","article-title":"Anaphase a: disassembling microtubules move chromosomes toward spindle poles","volume":"6","author":"Asbury","year":"2017","journal-title":"Biology"},{"key":"2022092808594342600_JCS259657C2","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1042\/BJ20042118","article-title":"Thiol-disulphide interchange in tubulin: kinetics and the effect on polymerization","volume":"389","author":"Britto","year":"2005","journal-title":"Biochem. 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