The nuclear localization of γ-tubulin is regulated by SadB-mediated phosphorylation.
Författare
Summary, in English
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 E2Fs. The mechanism that regulates localization of γ-tubulin is currently unknown. Here, we describe 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 triggered formation of chromatin associated γ-tubulin complexes that moderates 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 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.
Avdelning/ar
- Molekylär patologi, Malmö
- Avdelningen för molekylärmedicin och genterapi
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2014
Språk
Engelska
Sidor
21360-21373
Publikation/Tidskrift/Serie
Journal of Biological Chemistry
Volym
289
Issue
31
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Biochemistry and Molecular Biology
Ämne
- Cancer and Oncology
- Hematology
Status
Published
Forskningsgrupp
- Molecular Pathology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1083-351X