CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis.
Centrioles are essential for the assembly of both centrosomes and cilia. Centriole biogenesis occurs once and only once per cell cycle and is temporally coordinated with cell-cycle progression, ensuring the formation of the right number of centrioles at the right time. The formation of new daughter centrioles is guided by a pre-existing, mother centriole. The proximity between mother and daughter centrioles was proposed to restrict new centriole formation until they separate beyond a critical distance. Paradoxically, mother and daughter centrioles overcome this distance in early mitosis, at a time when triggers for centriole biogenesis Polo-like kinase 4 (PLK4) and its substrate STIL are abundant. Here we show that in mitosis, the mitotic kinase CDK1-CyclinB binds STIL and prevents formation of the PLK4-STIL complex and STIL phosphorylation by PLK4, thus inhibiting untimely onset of centriole biogenesis. After CDK1-CyclinB inactivation upon mitotic exit, PLK4 can bind and phosphorylate STIL in G1, allowing pro-centriole assembly in the subsequent S phase. Our work shows that complementary mechanisms, such as mother-daughter centriole proximity and CDK1-CyclinB interaction with centriolar components, ensure that centriole biogenesis occurs once and only once per cell cycle, raising parallels to the cell-cycle regulation of DNA replication and centromere formation.
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal. Electronic address: zsihem@igc.gulbenkian.pt.
Sihem
S
Zitouni
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal. Electronic address: mfrancia@igc.gulbenkian.pt.
Maria E
ME
Francia
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Filipe
F
Leal
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Susana
S
Montenegro Gouveia
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Catarina
C
Nabais
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Paulo
P
Duarte
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Samuel
S
Gilberto
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Daniela
D
Brito
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Tyler
T
Moyer
Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany.
Steffi
S
Kandels-Lewis
Center for Frontier Research, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Midori
M
Ohta
Center for Frontier Research, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Daiju
D
Kitagawa
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Andrew J
AJ
Holland
Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany; Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, and CNRS UMR 8197, 46 Rue d'Ulm, Paris 75005, France.
Eric
E
Karsenti
Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, France.
Thierry
T
Lorca
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
Mariana
M
Lince-Faria
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal. Electronic address: mdias@igc.gulbenkian.pt.
Mónica
M
Bettencourt-Dias
D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002502:Centrioles / Q000502:physiology*; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D047908:Intracellular Signaling Peptides and Proteins; C071236:STIL protein, human; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human
CDK; PLK4; STIL; centriole duplication; centrosome; licensing; mitosis