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
References [+] :
Bobinnec,
Centriole disassembly in vivo and its effect on centrosome structure and function in vertebrate cells.
1999,
Pubmed
Bobinnec,
Centriole disassembly in vivo and its effect on centrosome structure and function in vertebrate cells.
1999,
Pubmed
Eckerdt,
Kicking off the polo game.
2008,
Pubmed
Ferguson,
The cyclin A centrosomal localization sequence recruits MCM5 and Orc1 to regulate centrosome reduplication.
2010,
Pubmed
Ganem,
A mechanism linking extra centrosomes to chromosomal instability.
2009,
Pubmed
Guderian,
Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation.
2010,
Pubmed
Habedanck,
The Polo kinase Plk4 functions in centriole duplication.
2005,
Pubmed
Hammond,
Tubulin modifications and their cellular functions.
2008,
Pubmed
Hemerly,
Orc1 controls centriole and centrosome copy number in human cells.
2009,
Pubmed
Hinchcliffe,
Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts.
1999,
Pubmed
,
Xenbase
Khodjakov,
De novo formation of centrosomes in vertebrate cells arrested during S phase.
2002,
Pubmed
La Terra,
The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation.
2005,
Pubmed
Leung,
The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization.
2002,
Pubmed
Liu,
Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor.
2005,
Pubmed
,
Xenbase
Loncarek,
Ab ovo or de novo? Mechanisms of centriole duplication.
2009,
Pubmed
Maller,
Spindle formation and cleavage in Xenopus eggs injected with centriole-containing fractions from sperm.
1976,
Pubmed
,
Xenbase
Nebreda,
The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extracts of Xenopus oocytes and eggs.
1993,
Pubmed
,
Xenbase
Nigg,
Centrosome duplication: of rules and licenses.
2007,
Pubmed
Peel,
Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation.
2007,
Pubmed
Qian,
Activated polo-like kinase Plx1 is required at multiple points during mitosis in Xenopus laevis.
1998,
Pubmed
,
Xenbase
Rodrigues-Martins,
Revisiting the role of the mother centriole in centriole biogenesis.
2007,
Pubmed
Salisbury,
A mechanistic view on the evolutionary origin for centrin-based control of centriole duplication.
2007,
Pubmed
Schmidt,
Cytostatic factor: an activity that puts the cell cycle on hold.
2006,
Pubmed
,
Xenbase
Swallow,
Sak/Plk4 and mitotic fidelity.
2005,
Pubmed
Tunquist,
Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs.
2003,
Pubmed
,
Xenbase
Watanabe,
Independent inactivation of MPF and cytostatic factor (Mos) upon fertilization of Xenopus eggs.
1991,
Pubmed
,
Xenbase