title: The nuclear localization of γ-tubulin is regulated by SadB-mediated phosphorylation.
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 Ser(385) 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 Ala(385)-γ-tubulin but were enhanced by expression of SadB, wild-type γ-tubulin, or a phosphomimetic Asp(385)-γ-tubulin mutant. Our results demonstrate that SadB kinases regulate the cellular localization of γ-tubulin and thereby control S-phase progression.
authors.affiliation: From the Division of Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors.forename: Greta
authors.initials: G
authors.lastname: Eklund
authors.affiliation: From the Division of Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lang
authors.affiliation: From the Division of Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Glindre
authors.affiliation: From the Division of Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Ehlén
authors.affiliation: From the Division of Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden maria.alvarado-kristensson@med.lu.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarado-Kristensson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D017931:DNA Primers; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000378:metabolism* / Q000502:physiology
chemical_list: D017931:DNA Primers; D014404:Tubulin; D011494:Protein Kinases
keywords: Cell Cycle; Centrosome; Nucleus; Phosphorylation; Tubulin