Centriole duplication: A lesson in self-control.

Cell Cycle
Andrew J HollandDon W Cleveland

Abstract

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.

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Citations

Nov 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Andrew J HollandDon W Cleveland
Jul 23, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·S A Godinho, D Pellman
Jul 23, 2014·The Journal of Cell Biology·Erich J KushnerVictoria L Bautch
Jan 7, 2015·Cell Cycle·Yann ThomasVéronique Baldin
Apr 18, 2015·Frontiers in Cell and Developmental Biology·Tomer Avidor-ReissKyoung H Jo
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Aug 5, 2014·Breast Cancer Research and Treatment·Pascal FinettiFrançois Bertucci
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Aug 21, 2019·Cell Death & Disease·Min LiYuehong Yang
Jul 2, 2020·Signal Transduction and Targeted Therapy·Qi WuSi Sun
Jan 14, 2018·Molecular Cancer Research : MCR·Ryan A DenuNihal Ahmad
Feb 15, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·J PriyangaDipita Bhakta-Guha

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