SADB phosphorylation of gamma-tubulin regulates centrosome duplication.
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.
Alvarado-Kristensson
María
M
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain. maria.alvarado-kristensson@med.lu.se
Rodríguez
María Josefa
MJ
Silió
Virginia
V
Valpuesta
José M
JM
Carrera
Ana C
AC
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D018385:Centrosome / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000201:enzymology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D014404:Tubulin; D010768:Phosphoserine; C523084:BRSK1 protein, human; C496826:Brsk1 protein, mouse; D017346:Protein Serine-Threonine Kinases