Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication.
Duplication of the centrosome is well controlled during faithful cell division while deregulation of this process leads to supernumary centrosomes, chromosome missegregation and aneuploidy, a hallmark of many cancer cells. We previously reported that Polo-like kinase 2 (Plk2) is activated near the G1/S phase transition, and regulates the reproduction of centrosomes. In search for Plk2 interacting proteins we have identified NPM/B23 (Nucleophosmin) as a novel Plk2 binding partner. We find that Plk2 and NPM/B23 interact in vitro in a Polo-box dependent manner. An association between both proteins was also observed in vivo. Moreover, we show that Plk2 phosphorylates NPM/B23 on serine 4 in vivo in S-phase. Notably, expression of a non-phosphorylatable NPM/B23 S4A mutant interferes with centriole reduplication in S-phase arrested cells and leads to a dilution of centriole numbers in unperturbed U2OS cells. The corresponding phospho-mimicking mutants have the opposite effect and their expression leads to the accumulation of centrioles. These findings suggest that NPM/B23 is a direct target of Plk2 in the regulation of centriole duplication and that phosphorylation on serine 4 can trigger this process.
Krause
Annekatrin
A
Cell Cycle Control and Carcinogenesis, German Cancer Research Center, Heidelberg, Germany.
Hoffmann
Ingrid
I
D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D002502:Centrioles / Q000235:genetics*; D018385:Centrosome / Q000648:ultrastructure; D020440:Gene Duplication; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry*; D000090243:Nucleophosmin; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D012694:Serine / Q000737:chemistry
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D049452:Green Fluorescent Proteins; D012694:Serine; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases