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dc.contributor.authorLiang, K
dc.contributor.authorParedes, R
dc.contributor.authorCarmody, R
dc.contributor.authorEyers, P
dc.contributor.authorMeyer, Stefan
dc.contributor.authorMcCarthy, T
dc.contributor.authorKeeshan, K
dc.date.accessioned2016-11-01T14:14:03Z
dc.date.available2016-11-01T14:14:03Z
dc.date.issued2016-08-23
dc.identifier.citationHuman TRIB2 oscillates during the cell cycle and promotes ubiquitination and degradation of CDC25C. 2016, 17(9):1378 Int J Mol Scien
dc.identifier.issn1422-0067
dc.identifier.pmid27563873
dc.identifier.doi10.3390/ijms17091378
dc.identifier.urihttp://hdl.handle.net/10541/619994
dc.description.abstractTribbles homolog 2 (TRIB2) is a member of the mammalian Tribbles family of serine/threonine pseudokinases (TRIB1-3). Studies of TRIB2 indicate that many of the molecular interactions between the single Drosophila Tribbles (Trbl) protein and interacting partners are evolutionary conserved. In this study, we examined the relationship between TRIB2 and cell division cycle 25 (CDC25) family of dual-specificity protein phosphatases (mammalian homologues of Drosophila String), which are key physiological cell cycle regulators. Using co-immunoprecipitation we demonstrate that TRIB2 interacts with CDC25B and CDC25C selectively. Forced overexpression of TRIB2 caused a marked decrease in total CDC25C protein levels. Following inhibition of the proteasome, CDC25C was stabilized in the nuclear compartment. This implicates TRIB2 as a regulator of nuclear CDC25C turnover. In complementary ubiquitination assays, we show that TRIB2-mediated degradation of CDC25C is associated with lysine-48-linked CDC25C polyubiquitination driven by the TRIB2 kinase-like domain. A cell cycle associated role for TRIB2 is further supported by the cell cycle regulated expression of TRIB2 protein levels. Our findings reveal mitotic CDC25C as a new target of TRIB2 that is degraded via the ubiquitin proteasome system. Inappropriate CDC25C regulation could mechanistically underlie TRIB2 mediated regulation of cellular proliferation in neoplastic cells.
dc.languageENG
dc.language.isoenen
dc.rightsArchived with thanks to International journal of molecular sciencesen
dc.titleHuman TRIB2 oscillates during the cell cycle and promotes ubiquitination and degradation of CDC25C.en
dc.typeArticleen
dc.contributor.departmentLeukemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgowen
dc.identifier.journalInternational Journal of Molecular Sciencesen
refterms.dateFOA2018-12-17T14:44:28Z
html.description.abstractTribbles homolog 2 (TRIB2) is a member of the mammalian Tribbles family of serine/threonine pseudokinases (TRIB1-3). Studies of TRIB2 indicate that many of the molecular interactions between the single Drosophila Tribbles (Trbl) protein and interacting partners are evolutionary conserved. In this study, we examined the relationship between TRIB2 and cell division cycle 25 (CDC25) family of dual-specificity protein phosphatases (mammalian homologues of Drosophila String), which are key physiological cell cycle regulators. Using co-immunoprecipitation we demonstrate that TRIB2 interacts with CDC25B and CDC25C selectively. Forced overexpression of TRIB2 caused a marked decrease in total CDC25C protein levels. Following inhibition of the proteasome, CDC25C was stabilized in the nuclear compartment. This implicates TRIB2 as a regulator of nuclear CDC25C turnover. In complementary ubiquitination assays, we show that TRIB2-mediated degradation of CDC25C is associated with lysine-48-linked CDC25C polyubiquitination driven by the TRIB2 kinase-like domain. A cell cycle associated role for TRIB2 is further supported by the cell cycle regulated expression of TRIB2 protein levels. Our findings reveal mitotic CDC25C as a new target of TRIB2 that is degraded via the ubiquitin proteasome system. Inappropriate CDC25C regulation could mechanistically underlie TRIB2 mediated regulation of cellular proliferation in neoplastic cells.


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