title: Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152.
abstract: Centrosomes play an important role in various cellular processes, including spindle formation and chromosome segregation. They are composed of two orthogonally arranged centrioles, whose duplication occurs only once per cell cycle. Accurate control of centriole numbers is essential for the maintenance of genomic integrity. Although it is well appreciated that polo-like kinase 4 (Plk4) plays a central role in centriole biogenesis, how it is recruited to centrosomes and whether this step is necessary for centriole biogenesis remain largely elusive. Here we showed that Plk4 localizes to distinct subcentrosomal regions in a temporally and spatially regulated manner, and that Cep192 and Cep152 serve as two distinct scaffolds that recruit Plk4 to centrosomes in a hierarchical order. Interestingly, Cep192 and Cep152 competitively interacted with the cryptic polo box of Plk4 through their homologous N-terminal sequences containing acidic-α-helix and N/Q-rich motifs. Consistent with these observations, the expression of either one of these N-terminal fragments was sufficient to delocalize Plk4 from centrosomes. Furthermore, loss of the Cep192- or Cep152-dependent interaction with Plk4 resulted in impaired centriole duplication that led to delayed cell proliferation. Thus, the spatiotemporal regulation of Plk4 localization by two hierarchical scaffolds, Cep192 and Cep152, is critical for centriole biogenesis.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Anil
authors.initials: A
authors.lastname: Shukla
authors.forename: Sunho
authors.initials: S
authors.lastname: Choi
authors.forename: Ravichandran N
authors.initials: RN
authors.lastname: Murugan
authors.forename: Jin H
authors.initials: JH
authors.lastname: Lee
authors.forename: Mija
authors.initials: M
authors.lastname: Ahn
authors.forename: Kunsoo
authors.initials: K
authors.lastname: Rhee
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Bang
authors.forename: Bo Y
authors.initials: BY
authors.lastname: Kim
authors.forename: Jadranka
authors.initials: J
authors.lastname: Loncarek
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Erikson
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D015151:Immunoblotting; D047468:Immunoprecipitation; D016086:Lentivirus; D016296:Mutagenesis; D009841:Oligonucleotides / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: C551028:CEP152 protein, human; D018797:Cell Cycle Proteins; C526596:Cep192 protein, human; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D009841:Oligonucleotides; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases