{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:04:47Z","timestamp":1791317087712,"version":"4.3.1"},"reference-count":84,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T00:00:00Z","timestamp":1447200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Greek Secretariat for Research and Technology","award":["03ED778"],"award-info":[{"award-number":["03ED778"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Neurofibromatosis type\u20101 (NF\u20101) is caused by mutations in the tumor suppressor gene <jats:italic>NF1;<\/jats:italic> its protein product neurofibromin is a RasGTPase\u2010activating protein, a property that has yet to explain aneuploidy, most often observed in astrocytes in NF\u20101. Here, we provide a mechanistic model for the regulated nuclear import of neurofibromin during the cell cycle and for a role in chromosome congression. Specifically, we demonstrate that neurofibromin, phosphorylated on Ser2808, a residue adjacent to a nuclear localization signal in the C\u2010terminal domain (CTD), by Protein Kinase C\u2010epsilon (PKC\u2010\u03b5), accumulates in a Ran\u2010dependent manner and through binding to lamin in the nucleus at G2 in glioblastoma cells. Furthermore, we identify CTD as a tubulin\u2010binding domain and show that a phosphomimetic substitution of its Ser2808 results in a predominantly nuclear localization. Confocal analysis shows that endogenous neurofibromin localizes on the centrosomes at interphase, as well as on the mitotic spindle, through direct associations with tubulins, in glioblastoma cells and primary astrocytes. More importantly, analysis of mitotic phenotypes after siRNA\u2010mediated depletion shows that acute loss of this tumor suppressor protein leads to aberrant chromosome congression at the metaphase plate. Therefore, neurofibromin protein abundance and nuclear import are mechanistically linked to an error\u2010free chromosome congression.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13401-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nConcerned with neurofibromin's, a tumor suppressor, mechanism of action, we demonstrate in astrocytic cells that its synthesis, phosphorylation by Protein Kinase C\u2010\u03b5 on Ser2808 (a residue adjacent to a nuclear localization sequence), and nuclear import are cell cycle\u2010dependent, being maximal at G2. During mitosis, neurofibromin is an integral part of the spindle, while its depletion leads to aberrant chromosome congression, possibly explaining the development of chromosomal instability in Neurofibromatosis type\u20101.<\/jats:p><jats:p><jats:bold>Read the Editorial Highlight for this article on page<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/jnc.13435\">11<\/jats:ext-link>.<\/jats:p><jats:p><jats:bold>Cover Image for this issue: doi:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/jnc.13300\">10.1111\/jnc.13300<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13401","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T08:03:19Z","timestamp":1445500999000},"page":"78-91","source":"Crossref","is-referenced-by-count":39,"title":["Nuclear import mechanism of neurofibromin for localization on the spindle and function in chromosome congression"],"prefix":"10.1111","volume":"136","author":[{"given":"Xeni","family":"Koliou","sequence":"first","affiliation":[{"name":"Basic Research Center Biomedical Research Foundation of the Academy of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Fedonidis","sequence":"additional","affiliation":[{"name":"Basic Research Center Biomedical Research Foundation of the Academy of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Kalpachidou","sequence":"additional","affiliation":[{"name":"Basic Research Center Biomedical Research Foundation of the Academy of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Mangoura","sequence":"additional","affiliation":[{"name":"Basic Research Center Biomedical Research Foundation of the Academy of Athens Athens 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