Centriole duplication: A lesson in self-control.
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 and is associated with tumorigenesis in flies. By contrast, haploinsufficiency of Plk4 promotes 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.
Holland
Andrew J
AJ
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Lan
Weijie
W
Cleveland
Don W
DW
D000595:Amino Acid Sequence; D000818:Animals; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D042822:Genomic Instability; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability
C088051:Plk4 protein, mouse; D017346:Protein Serine-Threonine Kinases