The nuclear localization of γ-tubulin is regulated by SadB-mediated phosphorylation.

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The nuclear localization of γ-tubulin is regulated by SadB-mediated phosphorylation. / Eklund, Greta; Lang, Stefan; Glindre, Johan; Ehlén, Åsa; Alvarado-Kristensson, Maria.

I: Journal of Biological Chemistry, Vol. 289, Nr. 31, 2014, s. 21360-21373.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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T1 - The nuclear localization of γ-tubulin is regulated by SadB-mediated phosphorylation.

AU - Eklund, Greta

AU - Lang, Stefan

AU - Glindre, Johan

AU - Ehlén, Åsa

AU - Alvarado-Kristensson, Maria

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M114.562389

DO - 10.1074/jbc.M114.562389

M3 - Article

C2 - 24942739

VL - 289

SP - 21360

EP - 21373

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 31

ER -