dc.contributor.author | Ohba, Shigeo | |
dc.contributor.author | Tang, Yongjian | |
dc.contributor.author | Johannessen, Tor-Christian Aase | |
dc.contributor.author | Mukherjee, Joydeep | |
dc.date.accessioned | 2023-03-21T14:19:44Z | |
dc.date.available | 2023-03-21T14:19:44Z | |
dc.date.created | 2022-06-09T17:59:33Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 2234-943X | |
dc.identifier.uri | https://hdl.handle.net/11250/3059577 | |
dc.description.abstract | PKM2 is a phosphotyrosine-binding glycolytic enzyme upregulated in many cancers, including glioma, and contributes to tumor growth by regulating cell cycle progression. We noted, however, that in multiple glioma cell lines, PKM2 knock-down resulted in an accumulation of cells in G2-M phase. Moreover, PKM2 knock-down decreased Cdk1 activity while introducing a constitutively active Cdk1 reversed the effects of PKM2 knock-down on cell cycle progression. The means by which PKM2 increases Cdk1 activity have not been described. Transient interaction of T14/Y15-phosphorylated Cdk1 with cyclin B allows Cdk7-mediated pT161 Cdk1 phosphorylation followed by cdc25C-mediated removal of pT14/Y15 and activation of Cdk1 in cycling cells. In the present course of investigation, PKM2 modulation did not influence Cdk7 activity, but phosphotyrosine binding forms of PKM2 co-immunoprecipitated with pY15-containing Cdk1-cyclinB and enhanced formation of active pT161 Cdk1-cyclin B complexes. Moreover, exogenous expression of phosphotyrosine binding forms of PKM2 reversed the effects of PKM2 knock-down on G2-M arrest. We here show that PKM2 binds and stabilize otherwise transient pY15-containing Cdk1-cyclinB complexes that in turn facilitate Cdk1-cyclin B activation and entry of cells into mitosis. These results, therefore, establish metabolic enzyme PKM2 as a direct interactor and activator of Cdk1-cyclin B complex and thereby directly controls mitotic progression and the growth of brain tumor cells. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Frontiers | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | PKM2 Interacts With the Cdk1-CyclinB Complex to Facilitate Cell Cycle Progression in Gliomas | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2022 The Author(s) | en_US |
dc.source.articlenumber | 844861 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.3389/fonc.2022.844861 | |
dc.identifier.cristin | 2030616 | |
dc.source.journal | Frontiers in Oncology | en_US |
dc.identifier.citation | Frontiers in Oncology. 2022, 12, 844861. | en_US |
dc.source.volume | 12 | en_US |