Centriole duplication A lesson in self-control

• Published in: Cell cycle (Georgetown, Tex.) Vol. 9; no. 14; pp. 2803 - 2808
• Main Authors: Holland, Andrew J., Lan, Weijie, Cleveland, Don W.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 15.07.2010; Landes Bioscience
• Subjects: Amino Acid Sequence; Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Centrioles - metabolism; Centrosome - metabolism; Cycle; Extra View; Genomic Instability; Landes; Mice; Mitosis; Molecular Sequence Data; Organogenesis; Protein Stability; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - metabolism; Proteins
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.9.14.12184

In interphase and mitosis, centrosomes play a major role in the spatial organization of the microtubule network. Alterations in centrosome number and structure are associated with genomic instability and occur in many cancers. Centrosome duplication is controlled by centriole replication. In most dividing animal cells, centrioles duplicate only once per cell cycle at a site adjacent to existing centrioles. The conserved protein kinase Polo-like kinase 4 (Plk4) has a key role in controlling centriole biogenesis. Overexpression of Plk4 drives centrosome amplification, leading to genomic instability and the formation of tumors in flies. By contrast, haploinsufficiency of Plk4 causes cytokinesis failure leading to an increased incidence of tumors in mice. Recent studies have shown that Plk4 is a low abundance protein whose stability is linked to the activity of the enzyme. We discuss how this autoregulatory feedback loop acts to limit the damaging effects caused by too much or too little Plk4.