XB-ART-42854
Curr Biol
March 8, 2011;
21
(5):
428-32.
Identification of a polo-like kinase 4-dependent pathway for de novo centriole formation.
Abstract
Supernumerary centrosomes are a key cause of genomic instability in cancer cells. New centrioles can be generated by duplication with a mother
centriole as a platform or, in the absence of preexisting centrioles, by formation de novo. Polo-like kinase 4 (
Plk4) regulates both modes of
centriole biogenesis, and
Plk4 deregulation has been linked to tumor development. We show that
Plx4, the Xenopus homolog of mammalian
Plk4 and Drosophila Sak, induces de novo
centriole formation in vivo in activated oocytes and in
egg extracts, but not in immature or in vitro matured oocytes. Both kinase activity and the polo-box domain of
Plx4 are required for de novo
centriole biogenesis. Polarization microscopy in "cycling"
egg extracts demonstrates that de novo
centriole formation is independent of
Cdk2 activity, a major difference compared to template-driven
centrosome duplication that is linked to the nuclear cycle and requires cyclinA/E/
Cdk2. Moreover, we show that the
Mos-
MAPK pathway blocks
Plx4-dependent de novo
centriole formation before fertilization, thereby ensuring paternal inheritance of the
centrosome. The results define a new system for studying the biochemical and molecular basis of de novo
centriole formation and
centriole biogenesis in general.
PubMed ID:
21353560
PMC ID:
PMC3093158
Article link:
Curr Biol
Grant support:
[+]
Species referenced:
Xenopus laevis
Genes referenced:
cdk2
mapk1
mos
plk4
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