The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle

Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centriole duplication occurs once per cell cycle and is controlled by Polo-like kinase 4 (Plk4). We showed previously that Plk4 phosphorylates itself to promote its degradat...

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Bibliographic Details
Published in:Genes & development 2012-12, Vol.26 (24), p.2684-2689
Main Authors: Holland, Andrew J, Fachinetti, Daniele, Zhu, Quan, Bauer, Manuel, Verma, Inder M, Nigg, Erich A, Cleveland, Don W
Format: Article
Language:English
Subjects:
Cell Cycle - physiology
Cell Division - genetics
Cell Line
Cell Proliferation
Centrosome - physiology
Enzyme Stability - physiology
Gene Targeting
Homeostasis - physiology
Humans
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Research Communication
Tumor Suppressor Protein p53 - metabolism
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Summary:Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centriole duplication occurs once per cell cycle and is controlled by Polo-like kinase 4 (Plk4). We showed previously that Plk4 phosphorylates itself to promote its degradation by the proteasome. Here we demonstrate that this autoregulated instability controls the abundance of endogenous Plk4. Preventing Plk4 autoregulation causes centrosome amplification, stabilization of p53, and loss of cell proliferation; moreover, suppression of p53 allows growth of cells carrying amplified centrosomes. Plk4 autoregulation thus guards against genome instability by limiting centrosome duplication to once per cell cycle.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.207027.112