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dc.contributor.authorLaviolette, Laura A.en_US
dc.contributor.authorWilson, Jonasen_US
dc.contributor.authorKoller, Juliaen_US
dc.contributor.authorNeil, Christopheren_US
dc.contributor.authorHulick, Peteren_US
dc.contributor.authorRejtar, Tomasen_US
dc.contributor.authorKarger, Barryen_US
dc.contributor.authorTeh, Bin Teanen_US
dc.contributor.authorIliopoulos, Othonen_US
dc.date.accessioned2014-02-18T18:11:32Z
dc.date.issued2013en_US
dc.identifier.citationLaviolette, Laura A., Jonas Wilson, Julia Koller, Christopher Neil, Peter Hulick, Tomas Rejtar, Barry Karger, Bin Tean Teh, and Othon Iliopoulos. 2013. “Human Folliculin Delays Cell Cycle Progression through Late S and G2/M-Phases: Effect of Phosphorylation and Tumor Associated Mutations.” PLoS ONE 8 (7): e66775. doi:10.1371/journal.pone.0066775. http://dx.doi.org/10.1371/journal.pone.0066775.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11717581
dc.description.abstractThe Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN), and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn–/– mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcnflox/flox). The reintroduction of tumor-associated FLCN mutants (FLCN ΔF157, FLCN 1–469 or FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0066775en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708955/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectGeneticsen
dc.subjectCancer Geneticsen
dc.subjectGene Functionen
dc.subjectGenetic Mutationen
dc.subjectMolecular Cell Biologyen
dc.subjectCell Divisionen
dc.subjectMitosisen
dc.subjectMedicineen
dc.subjectOncologyen
dc.subjectBasic Cancer Researchen
dc.subjectCancers and Neoplasmsen
dc.subjectUrologyen
dc.subjectRenal Canceren
dc.titleHuman Folliculin Delays Cell Cycle Progression through Late S and G2/M-Phases: Effect of Phosphorylation and Tumor Associated Mutationsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorLaviolette, Laura A.en_US
dc.date.available2014-02-18T18:11:32Z
dc.identifier.doi10.1371/journal.pone.0066775*
dash.contributor.affiliatedIliopoulos, Othon
dash.contributor.affiliatedLaviolette, Laura A.


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