The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation.
The CDK11 (cyclin-dependent kinase 11) gene has an internal ribosome entry site (IRES), allowing the expression of two protein kinases. The longer 110-kDa isoform is expressed at constant levels during the cell cycle and the shorter 58-kDa isoform is expressed only during G2 and M phases. By means of RNA interference (RNAi), we show that the CDK11 gene is required for mitotic spindle formation. CDK11 RNAi leads to mitotic checkpoint activation. Mitotic cells are arrested with short or monopolar spindles. gamma-Tubulin as well as Plk1 and Aurora A protein kinase levels are greatly reduced at centrosomes, resulting in microtubule nucleation defects. We show that the mitotic CDK11(p58) isoform, but not the CDK11(p110) isoform, associates with mitotic centrosomes and rescues the phenotypes resulting from CDK11 RNAi. This work demonstrates for the first time the role of CDK11(p58) in centrosome maturation and bipolar spindle morphogenesis.
Petretti
Clotilde
C
CNRS UMR 6061 Université de Rennes I, Equipe Labellisée Ligue Nationale Contre le Cancer, IFR140 GFAS, Faculté de Médecine, France.
Savoian
Matthew
M
Montembault
Emilie
E
Glover
David M
DM
Prigent
Claude
C
Giet
Régis
R
D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D018385:Centrosome / Q000201:enzymology* / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D010641:Phenotype; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D008941:Spindle Apparatus / Q000201:enzymology* / Q000502:physiology*; D000097869:Polo-Like Kinase 1
D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C447612:CDK11a protein, human