The Nuclear Localization of γ-Tubulin Is Regulated by SadB-mediated Phosphorylation |
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Authors: | Greta Eklund Stefan Lang Johan Glindre ?sa Ehlén Maria Alvarado-Kristensson |
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Institution: | From the Division of Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden |
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Abstract: | γ-Tubulin is an important cell division regulator that arranges microtubule assembly and mitotic spindle formation. Cytosolic γ-tubulin nucleates α- and β-tubulin in a growing microtubule by forming the ring-shaped protein complex γTuRC. Nuclear γ-tubulin also regulates S-phase progression by moderating the activities of E2 promoter-binding factors. The mechanism that regulates localization of γ-tubulin is currently unknown. Here, we demonstrate that the human Ser/Thr kinase SadB short localizes to chromatin and centrosomes. We found that SadB-mediated phosphorylation of γ-tubulin on Ser385 formed chromatin-associated γ-tubulin complexes that moderate gene expression. In this way, the C-terminal region of γ-tubulin regulates S-phase progression. In addition, chromatin levels of γ-tubulin were decreased by the reduction of SadB levels or expression of a non-phosphorylatable Ala385-γ-tubulin but were enhanced by expression of SadB, wild-type γ-tubulin, or a phosphomimetic Asp385-γ-tubulin mutant. Our results demonstrate that SadB kinases regulate the cellular localization of γ-tubulin and thereby control S-phase progression. |
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Keywords: | Cell Cycle Centrosome Nucleus Phosphorylation Tubulin |
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