The tumor suppressor CDKN3 controls mitosis

dc.contributor.authorNalepa, Grzegorz
dc.contributor.authorBarnholtz-Sloan, Jill
dc.contributor.authorEnzor, Rikki
dc.contributor.authorDey, Dilip
dc.contributor.authorHe, Ying
dc.contributor.authorGehlhausen, Jeff R.
dc.contributor.authorLehmann, Amalia S.
dc.contributor.authorPark, Su-Jung
dc.contributor.authorYang, Yanzhu
dc.contributor.authorYang, Xianlin
dc.contributor.authorChen, Shi
dc.contributor.authorGuan, Xiaowei
dc.contributor.authorChen, Yanwen
dc.contributor.authorRenbarger, Jamie
dc.contributor.authorYang, Feng-Chun
dc.contributor.authorParada, Luis F.
dc.contributor.authorClapp, Wade
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2025-05-07T10:36:44Z
dc.date.available2025-05-07T10:36:44Z
dc.date.issued2013
dc.description.abstractMitosis is controlled by a network of kinases and phosphatases. We screened a library of small interfering RNAs against a genome-wide set of phosphatases to comprehensively evaluate the role of human phosphatases in mitosis. We found four candidate spindle checkpoint phosphatases, including the tumor suppressor CDKN3. We show that CDKN3 is essential for normal mitosis and G1/S transition. We demonstrate that subcellular localization of CDKN3 changes throughout the cell cycle. We show that CDKN3 dephosphorylates threonine-161 of CDC2 during mitotic exit and we visualize CDC2(pThr-161) at kinetochores and centrosomes in early mitosis. We performed a phosphokinome-wide mass spectrometry screen to find effectors of the CDKN3-CDC2 signaling axis. We found that one of the identified downstream phosphotargets, CKβ phosphorylated at serine 209, localizes to mitotic centrosomes and controls the spindle checkpoint. Finally, we show that CDKN3 protein is down-regulated in brain tumors. Our findings indicate that CDKN3 controls mitosis through the CDC2 signaling axis. These results have implications for targeted anticancer therapeutics.
dc.eprint.versionFinal published version
dc.identifier.citationNalepa G, Barnholtz-Sloan J, Enzor R, et al. The tumor suppressor CDKN3 controls mitosis [published correction appears in J Cell Biol. 2013 Aug 19;202(4):717]. J Cell Biol. 2013;201(7):997-1012. doi:10.1083/jcb.201205125
dc.identifier.urihttps://hdl.handle.net/1805/47848
dc.language.isoen_US
dc.publisherRockefeller University Press
dc.relation.isversionof10.1083/jcb.201205125
dc.relation.journalThe Journal of Cell Biology
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.sourcePMC
dc.subjectCyclin-dependent kinase inhibitor proteins
dc.subjectKinetochores
dc.subjectMitosis
dc.subjectCentrosome
dc.titleThe tumor suppressor CDKN3 controls mitosis
dc.typeArticle
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