Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 31, Pages 21360-21373Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.562389
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Funding
- Swedish Research Council
- Swedish Cancer Society
- Swedish childhood cancer foundation
- Royal Physiographic Society in Lund
- Gradfoordska Foundation
- Gunnar Nilsson Foundation
- Gyllenstiernska Krapperupsstiftelsen
- Skane University Hospital in Malmo Cancer Research Fund
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gamma-Tubulin is an important cell division regulator that arranges microtubule assembly and mitotic spindle formation. Cytosolic gamma-tubulin nucleates alpha- and beta-tubulin in a growing microtubule by forming the ring-shaped protein complex gamma TuRC. Nuclear gamma-tubulin also regulates S-phase progression by moderating the activities of E2 promoter-binding factors. The mechanism that regulates localization of gamma-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 gamma-tubulin on Ser385 formed chromatin-associated gamma-tubulin complexes that moderate gene expression. In this way, the C-terminal region of gamma-tubulin regulates S-phase progression. In addition, chromatin levels of gamma-tubulin were decreased by the reduction of SadB levels or expression of a non-phosphorylatable Ala(385)-gamma-tubulin but were enhanced by expression of SadB, wild-type gamma-tubulin, or a phosphomimetic Asp(385)-gamma-tubulin mutant. Our results demonstrate that SadB kinases regulate the cellular localization of gamma-tubulin and thereby control S-phase progression.
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