Biology Open · 2011 · 45 citations · 37 references
Life SciencesBiochemistryMolecular BiologyCell CycleCell DivisionMolecular Cell BiologyCell Cycle BiochemistryCell Cycle ControlCell-cycle RegulationMitosisMitotic EntryMitotic ExitCell Cycle Control ProteinsMitosis RegulationMitotic Entry ControlMitotic Entry RegulationRegulation By E3 Ubiquitin LigasesUbiquitin BindingUbiquitin-mediated Cell Cycle ControlUbiquitin-mediated Cell-cycle Regulation
The cullin-RING family of ubiquitin ligases regulates diverse cellular functions, such as cell cycle control, via ubiquitylation of specific substrates. CUL3 targets its substrates through BTB proteins. Here we show that depletion of CUL3 and the BTB protein KLHL18 causes a delay in mitotic entry. Centrosomal activation of Aurora-A, a kinase whose activity is required for entry into mitosis, is also delayed in depleted cells. Moreover, we identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes. We propose that the CUL3-KLHL18 ligase regulates mitotic entry through an Aurora-A-dependent pathway.
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Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
Libor Macůrek, Arne Lindqvist, Dan Lim et al. · Nature · 2008 · 711 citations