Alvarado-Kristensson María, Rodríguez María Josefa, Silió Virginia, Valpuesta José M, Carrera Ana C
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
Nat Cell Biol. 2009 Sep;11(9):1081-92. doi: 10.1038/ncb1921. Epub 2009 Aug 2.
Symmetrical cell division requires duplication of DNA and protein content to generate two daughter cells. Centrosomes also duplicate during cell division, but the mechanism controlling this process is incompletely understood. We describe an alternative splice form of SadB encoding a short SADB Ser/Thr kinase whose activity fluctuates during the cell cycle, localizes to centrosomes, and controls centrosome duplication. Reduction of endogenous SADB levels diminished centrosome numbers, whereas enhanced SADB expression induced centrosome amplification. SADB exerted this action through phosphorylation of gamma-tubulin on Ser 131, as expression of a phosphomimetic Ser 131-to-Asp gamma-tubulin mutant alone increased centrosome numbers, whereas non-phosphorylatable Ala 131-gamma-tubulin impaired centrosome duplication. We propose that SADB kinase activity controls centrosome homeostasis by regulating phosphorylation of gamma-tubulin.
对称细胞分裂需要复制DNA和蛋白质含量以产生两个子细胞。中心体在细胞分裂期间也会复制，但控制这一过程的机制尚未完全了解。我们描述了SadB的一种可变剪接形式，它编码一种短的SADB丝氨酸/苏氨酸激酶，其活性在细胞周期中波动，定位于中心体，并控制中心体复制。内源性SADB水平的降低减少了中心体数量，而增强的SADB表达则诱导中心体扩增。SADB通过对γ-微管蛋白的丝氨酸131进行磷酸化发挥这一作用，因为单独表达模拟磷酸化的丝氨酸131突变为天冬氨酸的γ-微管蛋白突变体增加了中心体数量，而非磷酸化的丙氨酸131-γ-微管蛋白则损害了中心体复制。我们提出，SADB激酶活性通过调节γ-微管蛋白的磷酸化来控制中心体的稳态。
