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Cold Spring Harbor Laboratory Press, Genes & Development, 24(26), p. 2684-2689, 2012

DOI: 10.1101/gad.207027.112

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

Journal article published in 2012 by Holland Aj, Andrew J. Holland, Daniele Fachinetti, Quan Zhu, Manuel Bauer, Verma Im, Inder M. Verma, Nigg Ea, Erich A. Nigg ORCID, Don W. Cleveland ORCID, Cleveland Dw
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.